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Polysaccharide of Alocasia cucullata Exerts Antitumor Effect by Regulating Bcl-2, Caspase-3 and ERK1/2 Expressions during Long-Time Administration

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Chinese Journal of Integrative Medicine 2024年第1期30卷 52-61页

作者： ZHOU Qi-chun XIAO Shi-lin LIN Ru-kun LI Chan CHEN Zhi-jie CHEN Yi-fei LUO Chao-hua MO Zhi-xian LIN Ying-bo School of Traditional Chinese Medicine Southern Medical UniversityGuangzhou(510515)China clinical and basic research team of tcm prevention and treatment of non-small cell lung cancer the Second Clinical College of Guangzhou University of Chinese MedicineGuangzhou(510120)China Department of Chinese Medicine Zhujiang Hospital Affiliated to Southern Medical UniversityGuangzhou(510282)China Department of Pharmacy Jiangmen Central HospitalJiangmen(529000)China

Objective: To study the in vitro and in vivo antitumor effects of the polysaccharide of Alocasia cucullata(PAC) and the underlying mechanism. Methods: B16F10 and 4T1 cells were cultured with PAC of 40 μg/m L, and PAC was withdrawn after 40 days of administration. The cell viability was detected by cell counting kit-8. The expression of Bcl-2 and Caspase-3 proteins were detected by Western blot and the expressions of ERK1/2 mRNA were detected by quantitative real-time polymerase chain reaction(qRT-PCR). A mouse melanoma model was established to study the effect of PAC during long-time administration. Mice were divided into 3 treatment groups: control group treated with normal saline, positive control group(LNT group) treated with lentinan at 100 mg/(kg·d), and PAC group treated with PAC at 120 mg/(kg·d). The pathological changes of tumor tissues were observed by hematoxylin-eosin staining. The cell apoptosis of tumor tissues was detected by TUNEL staining. Bcl-2 and Caspase-3 protein expressions were detected by immunohistochemistry, and the expressions of ERK1/2, JNK1 and p38 mRNA were detected by qRT-PCR. Results: In vitro, no strong inhibitory effects of PAC were found in various tumor cells after 48 or 72 h of administration. Interestingly however, after 40 days of cultivation under PAC, an inhibitory effect on B16F10 cells was found. Correspondingly, the long-time administration of PAC led to downregulation of Bcl-2 protein(P cells. The above results were verified by in vivo experiments. In addition, viability of B16F10 cells under long-time administration culture in vitro decreased after drug withdrawal, and similar results were also observed in 4T1 cells. Conclusions: Long-time administration of PAC can significantly inhibit viability and promote apoptosis of tumor cells, and had obvious antitumor effect in tumor-bearing mice.

关键词： polysaccharide of Alocasia cucullata tumor cells Bcl-2 Caspase-3 ERK1/2 Chinese medicine

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Exosome based miRNA delivery strategy for disease treatment

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Chinese Chemical Letters 2022年第4期33卷 1693-1704页

作者： Zhengwen Fang Xinyu Zhang Hai Huang Jun Wu School of Biomedical Engineering Sun Yat-sen UniversityShenzhen 518107China Department of Drug clinical Trial Institution National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital&Shenzhen HosptialChinese Academy of Medical Sciences and Peking Union Medical CollegeShenzhen 518116China Department of Urology Sun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangzhou 510220China

miRNA, which is a common non-coding RNA, can target various m RNAs to regulate their physiological activities. Therefore, mi RNAs play an important role in various physiological and pathological processes,and so they have been proposed as a powerful tool to treat different diseases efficiently. However, the characteristic of mi RNA degradation in vivo limits its further clinical application. Exosomes have the advantage of crossing the biological barrier and achieving long-distance communication with cells, so they are excellent vectors for mi RNAs. By studying the biogenesis of exosomes, the way for loading mi RNAs,the mechanism of targeting, and disease occurrence and development, it is confirmed that exosomes can enrich specific endogenous mi RNAs and regulate a variety of physiological activities, such as promoting cancer cell apoptosis, regulating lipid metabolism and promoting angiogenesis. It is shown that exosomes loaded with mi RNAs have good performance in the fields of cancer, neurodegenerative diseases,cardiovascular disease treatment, and regenerative medicine. In this paper, the application and research progress of exosomes carrying mi RNA in the above fields are systematically described.

关键词： Mirna Extracellular vesicles Drug carrier cancer therapy

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Fuzheng Kang'ai decoction(扶正抗癌方) inhibits cell proliferation,migration and invasion by modulating mir-21-5p/human phosphatase and tensin homology deleted on chromosome ten in lung cancer cells

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Journal of Traditional Chinese Medicine 2022年第3期42卷 344-352页

作者： LI Jinhua LIU Chunping ZHAO Yueyang WU Wanyin SUN Pengtao LI Longmei YANG Xiaobing ZHOU Yushu Department of Ultrasound Guangdong Provincial Hospital of Chinese Medicinethe Second Affiliated Hospital of Guangzhou University of Chinese MedicineGuangzhou 510120China Department of Ultrasound Institute of Ultrasound in Musculoskeletal Sports MedicineGuangdong Second Provincial General HospitalGuangzhou 510317China State Key Laboratory of Dampness Syndrome of Chinese Medicine Guangdong Provincial Hospital of Chinese MedicineThe Second Affiliated Hospital of Guangzhou University of Chinese MedicineGuangzhou 510120China Department of Hematology Guangdong Provincial Hospital of Chinese Medicinethe Second Affiliated Hospital of Guangzhou University of Chinese MedicineGuangzhou 510120China Department of Oncology Clinical and Basic Research Team of TCM Prevention and Treatment of NSCLCGuangdong Provincial Hospital of Chinese Medicinethe Second Affiliated Hospital of Guangzhou University of Chinese MedicineGuangzhou 510120China

OBJECTIVE:To elucidate the potential molecular mechanism by which Fuzheng Kang’ai decoction(扶正抗癌方,FZKA)inhibits proliferation,migration,and invasion of lung cancer ***:Varying FZKA concentrations were used to manage lung cancer cells(A549 and PC9).We employed:cell counting kit-8(CCK-8)and plate clone formation assays to examine the cell viability;flow cytometry(FCM)to analyze the cycle arrest;transwell and woundhealing assays to assess the cell invasion and migration,***,a quantitative real-time polymerase chain reaction(q RT-PCR)assay was adopted to evaluate the miR-21-5p *** protein expression analysis,we employed the Western blot *** miR-21-5p overexpression adenovirus vector harboring GFP was constructed and transfected into A549 and PC9,after which we explored the effect of FZKA on miR-21-5p ***:Notably,treatment with FZKA inhibited viability,clone-formation ability,invasion,and migration of lung cancer ***,FZKA markedly suppressed miR-21-5p expression but elevated the human phosphatase and tensin homology deleted on chromosome ten(PTEN)protein level in both A549 and PC9 ***-expression of miR-21-5p lowered PTEN protein ***,overexpressed miR-21-5p levels with adenovirus antagonized FZKA-upregulated PTEN protein ***:The present study demonstrates how FZKA modulates cell biological behaviors,for instance,it impedes the proliferation by upregulating PTEN expression with miR-21-5p as the *** findings unveil the potential novel molecular mechanisms from the micro RNA aspect by which FZKA suppresses the growth of human lung cancer cells.

关键词： lung neoplasms miR-21-5p PTEN phosphohydrolase Fuzheng Kang’ai decoction

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The role of exosomal long non-coding RNAs in cancer drug resistance

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cancer Drug Resistance 2019年第4期2卷 1178-1192页

作者： Mireia Cruz De los Santos Mihnea P.Dragomir George A.Calin Department of Experimental Therapeutics The University of Texas MD Anderson Cancer CenterHoustonTX 77054USA research Center for Functional Genomics Biomedicine and Translational MedicineIuliu Hatieganu University of Medicine and PharmacyCluj-Napoca 40015Romania Department of Surgery Fundeni Clinical HospitalCarol Davila University of Medicine and PharmacyBucharest 022328Romania Center for RNA Interference and non-coding RNAs The University of Texas MD Anderson Cancer CenterHoustonTX 77054USA

One of the major challenges in oncology is drug resistance,which triggers relapse and shortens patients’*** order to promote drug desensitization,cancer cells require the establishment of an ideal tumor microenvironment that accomplishes specific *** achieve this objective,cellular communication is a key ***,cells were believed to restrictively communicate by ligand-receptor binding,physical cell-to-cell interactions and ***,the crosstalk between tumor cells and stroma cells has also been recently reported to be mediated through exosomes,the smallest extracellular vesicles,which transport a plethora of functionally active molecules,such as:proteins,lipids,messenger RNA,DNA,microRNA or long non-coding RNA(lncRNAs).LncRNAs are RNA molecules greater than 200 base pairs that are deregulated in cancer and other *** lncRNAs are highly stable and can be found in several body fluids,being considered potential biomarkers for tumor liquid *** lncRNAs promote angiogenesis,cell proliferation and drug *** role of exosomal lncRNAs in drug resistance affects the main treatment strategies in oncology:chemotherapy,targeted therapy,hormone therapy and ***,knowing the molecular mechanisms by which exosomal lncRNA induce pharmacologic resistance could improve further drug development and identify drug resistance biomarkers.

关键词： Tumor microenvironment extracellular vesicles exosomes non-coding RNA long non-coding RNA drug resistance

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Characterization of 500 Chinese patients with cervical esophageal cancer by clinicopathological and treatment outcomes

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cancer Biology & Medicine 2020年第1期17卷 218-226页

作者： Peinan Chen Xueke Zhao Fuyou Zhou Xin Song Shoujia Hu Yan Jin Xianzeng Wang Xuena Han ZongminFan Ran Wang Bei Li Wenli Han Panpan Wang Jilin Li Lixin Wan Liguo Zhang Qide Bao Fubao Chang Yanru Qin Zhiwei Chang Jianwei Ku Haijun Yang Ling Yuan Jingli Ren Xuemin Li Lidong Wang State Key Laboratory of Esophageal cancer prevention&treatment and Henan Key Laboratory for Esophageal cancer research of The First Affiliated Hospital Zhengzhou UniversityZhengzhou 450052China Department of Thoracic Surgery Anyang Tumor HospitalAnyang 455000China Department of Histology and Embryology School of Basic Medical SciencesXinxiang Medical UniversityXinxiang 453000China Department of Thoracic Surgery Linzhou People's HospitalLinzhou 456550China Department of Pathology and Pathophysiology School of Basic Medical SciencesZhengzhou UniversityZhengzhou 450000China Department of Pathology Linzhou Esophageal Cancer HospitalLinzhou 456550China Department of Oncology Nanyang Central HospitalNanyang 473000China Department of Thoracic Surgery Xinxiang Central HospitalXinxiang 453000China Department of Oncology Anyang District HospitalAnyang 455000China Department of Thoracic Surgery Linzhou Center HospitalLinzhou 456550China Department of Oncology the First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450000China Department of Gastroenterology The Second Affiliated Hospital of Nanyang Medical CollegeNanyang 473000China Department of Pathology Anyang Tumor HospitalAnyang 455000China Department of Radiotherapy The Affiliated Cancer Hospital of Zhengzhou University(Henan Cancer Hospital)Zhengzhou 450000China Department of Pathology The Second Affiliated Hospital of Zhengzhou UniversityZhengzhou 450000China Department of Pathology Hebei Provincial Cixian People's HospitalCixian 056500China

Objective: There are no comprehensive studies on survival outcomes and optimal treatment protocols for cervical esophageal cancer(CEC), due to its rare clinical prevalence. Our objective was to determine the relationship between pathological characteristics, treatment protocols, and survival outcomes in Chinese CEC ***: A total of 500 Chinese CEC patients were selected from our 500,000 esophageal and gastric cardia carcinoma database(1973–2018). There were two main groups: patients treated with surgery, and patients receiving non-surgical treatments(radiotherapy, radiochemotherapy, and chemotherapy). The Chi-square test and Kaplan–Meier method were used to compare the continuous variables and ***: Among the 500 CEC patients, 278(55.6%) were male, and the median age was 60.9 ± 9.4 years. A total of 496 patients(99.2%) were diagnosed with squamous cell carcinoma. In 171(34.2%) patients who received surgery, 22(12.9%) had undergone laryngectomy. In 322(64.4%) patients who received non-surgical treatments, 245(76.1%) received radiotherapy. Stratified survival analysis showed that only T stage was related with survival outcomes for CEC patients in the surgical group, and the outcomes between laryngectomy and non-laryngectomy patients were similar. It was noteworthy that the 5-year survival rate was similar in CEC patients among the different groups treated with surgery, radiotherapy, chemotherapy, or radiochemotherapy(P = 0.244). Conclusions: The CEC patients had similar survival outcomes after curative esophagectomy and radiotherapy, including those with or without total laryngectomy. These findings suggest that radiotherapy could be the initial choice for treatment of Chinese CEC patients.

关键词： Cervical esophageal cancer survival esophagectomy radiochemotherapy

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Feiji Recipe inhibits the growth of lung cancer by modulating T-cell immunity through indoleamine-2,3-dioxygenase pathway in an orthotopic implantation model

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Journal of Integrative Medicine 2018年第4期16卷 283-289页

作者： Bin Luo Zu-jun Que Zhi-yi Zhou Qing Wang Chang-sheng Dong Yi Jiang Bing Hu Hui Shi Yu Jin Jian-wen Liu He-gen Li Lin Wang Jian-hui Tian Department of Oncology Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine Oncology Institute of Traditional Chinese Medicine Institute of TCM Oncology School of Pharmacy East China University of Science and Technology Department of Nephrology Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine

Objective： Escape from the body＇s immune response is a basic characteristic of lung cancer, and indoleamine-2,3-dioxygenase （IDO） plays a key role in mediating immune escape of non-small-cell lung cancer, which leads to recurrence and metastasis. Feiji Recipe, a compound Chinese herbal medicine, has the effect of stabilizing lesions and prolonging survival in patients with lung cancer. The purpose of this study was to investigate the mechanisms underlying the anticancer properties of Feiji Recipe. Methods： An orthotopic transplant model of mouse Lewis lung cancer, with stable expression of IDO gene, was established in C57BL/6 mice. Optical imaging was used to observe the effects of Feiji Recipe in the treatment of lung cancer in vivo. The effects of Feiji Recipe on the proliferation of mouse Lewis lung cancer cell line 2LL, 2LL-enhanced green fluorescent protein （2LL-EGFP） and 2LL-EGFP-IDO were investi- gated, and the apoptosis of T-cells was examined by 3-（4,5-dimethyl-2-thiazolyl）-2,5-diphenyl-2H-tetra zolium bromide using flow cytometry. Chemical composition of Feiji Recipe was validated by high- performance liquid chromatography. Results： Compared to the control group, the survival of animals treated with Feiji Recipe was significantly prolonged （P〈0.0074）, and the IDO protein level decreased （P=0.0072）; moreover, the percentages of CD4＋CD25＋ T-cells and Foxp3＋ T-cells were significantly decreased （P〈0.05）. The molecular mechanism of Feiji Recipe against lung cancer may relate to the regulation of immune cells, such as T-cells and reg- ulatory T-cells. Conclusion： The molecular mechanism of Feiji Recipe in treatment of lung cancer is to restore the function of T-cells in the cancer microenvironment through interfering with the IDO pathway.

关键词： Feiji Recipe Immune escape Orthotopic xenografts Indoleamine-2,3-dioxygenase

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