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Effects of oxaliplatin on DNA condensation

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Science China(Physics,Mechanics & Astronomy) 2014年第11期57卷 2114-2120页

作者： JU HaiPeng ZHANG HongYan LI Wei WANG PengYe Beijing National laboratory for Condensed Matter Physics and Key laboratory of Soft Matter Physics Institute of PhysicsChinese Academy of Sciences

In this paper the interactions between DNA and anti-cancer drug oxaliplatin were investigated by using magnetic *** dynamics of DNA condensation due to oxaliplatin was traced under various *** is found that torsion constraint in DNA enhances the ability of oxaliplatin for shortening *** transplatin helps oxaliplatin combine to DNA and increase the rate of DNA *** these results are consistent to the previously proposed model and are helpful for further investigation of interaction between DNA and oxaliplatin.

关键词： DNA condensation shortening torsion helpful constraint cisplatin analogues tethered traced

Effect of cisplatin on the Flexibility of Linear DNA

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Chinese Physics Letters 2011年第6期28卷 344-347页

作者： JI Chao ZHANG Ling-Yun HOU Xi-Miao DOU Shuo-Xing WANG Peng-Ye Key laboratory of Soft Matter Physics Beijing National Laboratory for Condensed Matter PhysicsInstitute of PhysicsChinese Academy of SciencesBeijing 100190

With the aid of an atomic force microscope(AFM),we study the interaction between linear DNA fragment and *** different cisplatin concentrations,the AFM used to observe the conformation of DNA has a gradual *** contour length,the end-to-end distance and the local bend angles of the linear DNA fragment can be accurately *** persistence length of DNA interacting with cisplatin is decreased with the increasing cisplatin ***,it is demonstrated that the local bend angles of DNA chains are increased by the binding interaction of cisplatin.

关键词： cisplatin concentration cisplatin

Local conformation transitions of linear DNA induced by cisplatin

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Chinese Science Bulletin 2014年第25期59卷 3085-3089页

作者： Chao Ji Lingyun Zhang Shuoxing Dou Pengye Wang Key laboratory of Soft Matter Physics Beijing National Laboratory for Condensed Matter Physics Institute of PhysicsChinese Academy of Sciences

cisplatin is the most successful anti-tumor drug,and its pharmacological property is generally considered to derive from the modification of DNA *** modifications of short DNA induced by cisplatin have already been ***,the conformation transitions induced by cisplatin are not *** the present letter,we have studied the effect of low-concentration cisplatin on DNA conformation by using AFM *** observed formations of micro-rod structures of linear DNA induced by cisplatin.A method is presented to quantitatively analyze the occurrence of micro-rod *** found that the formation of micro-rod structures depends on the DNA *** on the results,we proposed a physical mechanism to explain the local conformation transitions of DNA molecules under the influence of cisplatin.

关键词： DNA分子顺铂诱导构象转变线性结构改造原子力显微镜构象转换

Switchable nanoparticles complexing cisplatin for circumventing glutathione depletion in breast cancer chemotherapy

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Chinese Chemical Letters 2023年第5期34卷 414-419页

作者： Ming Chen Ying Xie Qian Luo Jiarui Xu Yuxin Ren Rui Liu Huihui Zhao Yuling Chen Hexuan Feng Yafei Du Jianwei Li Guiling Wang Wanliang Lu State Key laboratory of Natural and Biomimetic Drugs Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systemsand School of Pharmaceutical SciencesPeking UniversityBeijing 100191China

cisplatin is broad-spectrum chemotherapeutic agent that has been widely used for the treatment of a variety of malignant tumors including breast ***,the cisplatin chemoresistance,which derives from the inactivation by glutathione(GSH)depletion,remains a scientific issue to ***,we report a novel type of smart disulfide switchable nanoparticles complexing cisplatin(switch NPs-cisplatin)that is rationally designed,and engineered by synthesizing a hyaluronic acid disulfide bonded polyaspartic acid(HA-ss-Pasp)and complexing *** results showed that the switch NPs-cisplatin had a nanoscale of particle size(150 nm),higher drug encapsulation efficiency(>90%),and suitable drug release *** demonstrated evident pH responsiveness and GSH responsiveness,and targeting effect in the resistant breast cancer ***,they were able to block the cisplatin depletion by GSH in the resistant cancer cells,thereby circumventing the ***,switch NPs-cisplatin displayed a remarkable killing effect in the resistant breast cancer cells in vitro,and in the resistant breast cancer-bearing *** conclusion,switch NPs-cisplatin could be used as a smart formulation of cisplatin for overcoming the chemoresistance of breast *** present study also offers a universal drug delivery carrier platform for highly efficient but low systemic toxic chemotherapy.

关键词： Disulfide switchable nanoparticles pH responsiveness GSH depletion cisplatin chemoresistance Breast cancer

Concurrent silencing of TBCE and drug delivery to overcome platinum-based resistance in liver cancer

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Acta Pharmaceutica Sinica B 2023年第3期13卷 967-981页

作者： Senlin Li Siyu Chen Zhihui Dong Xingdong Song Xiuling Li Ziqi Huang Huiru Li Linzhuo Huang Ganyuan Zhuang Ran Lan Mingyan Guo Wende Li Phei Er Saw Lei Zhang Guangdong Provincial Key laboratory of Malignant Tumor Epigenetics and Gene Regulation Guangdong-Hong Kong Joint Laboratory for RNA MedicineSun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangzhou510120China Department of Hepatobiliary Surgery Sun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangzhou 510120China Guangdong laboratory Animals Monitoring Institute Guangdong Key Laboratory of Laboratory AnimalsGuangzhou510663China Department of Anesthesiology Sun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangzhou510120China

Platinum-based chemotherapy resistance is a key factor of poor prognosis and recurrence in hepatocellular carcinoma(HCC).Herein,RNAseq analysis revealed that elevated tubulin folding cofactor E(TBCE)expression is associated with platinum-based chemotherapy *** expression of TBCE contributes to worse prognoses and earlier recurrence among liver cancer ***,TBCE silencing significantly affects cytoskeleton rearrangement,which in turn increases cisplatin-induced cycle arrest and *** develop these findings into potential therapeutic drugs,endosomal pH-responsive nanoparticles(NPs)were developed to simultaneously encapsulate TBCE siRNA and cisplatin(DDP)to reverse this ***(siTBCE+DDP)concurrently silenced TBCE expression,increased cell sensitivity to platinum treatment,and subsequently resulted in superior anti-tumor effects both in vitro and in vivo in orthotopic and patient-derived xenograft(PDX)*** together,NP-mediated delivery and the co-treatment of siTBCE+DDP proved to be effective in reversing chemotherapy resistance of DDP in multiple tumor models.

关键词： Hepatocellular carcinoma Tubulin folding cofactor E Chemoresistance siRNA delivery RNA interference Nanoparticle Combination therapy Nanomedicine

The Zuo Jin Wan Formula increases chemosensitivity of human primary gastric cancer cells by AKT mediated mitochondrial translocation of cofilin-1

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Chinese Journal of Natural Medicines 2019年第3期17卷 198-208页

作者： SUN Meng-Yao WANG Dan-Dan SUN Jian ZHAO Xiao-Hua CAI Si WU Qiu-Xue JIE Tao NI Zhen-Hua SUN Jian-Yue TANG Qing-Feng Department of Clinical laboratory and Central laboratory Putuo Hospital Shanghai University of Traditional Chinese Medicine Institute of Interdisciplinary Medical Sciences Shanghai University of Traditional Chinese Medicine Department of Clinical laboratory Shuguang Hospital Shanghai University of Traditional Chinese Medicine Department of Pediatrics Putuo Hospital Shanghai University of Traditional Chinese Medicine

Resistance to cisplatin(DDP)-based chemotherapy is a major cause of treatment failure in human gastric cancer(GC). It is necessary to identify the drugs to re-sensitize GC cells to DDP. In our previous research, Zuo Jin Wan Formula(ZJW) has been proved could increase the mitochondrial apoptosis via cofilin-1 in a immortalized cell line, SGC-7901/DDP. Due to the immortalized cells may still difficult highly recapitulate the important molecular events in vivo, primary GC cells model derived from clinical patient was constructed in the present study to further evaluate the effect of ZJW and the underlying molecular mechanism. Immunofluorescent staining was used to indentify primary cultured human GC cells. Western blotting was carried out to detect the protein expression. Cell Counting Kit-8(CCK-8) was used to evaluate cell proliferation. Flow cytometry analysis was performed to assess cell apoptosis. ZJW inhibited proliferation and induced apoptosis in primary DDP-resistant GC cells. Notably, the apoptosis in GC cells was mediated by inducing cofilin-1 mitochondrial translocation, down-regulating Bcl-2 and up-regulating Bax expression. Surprisingly, the level of p-AKT protein was higher in DDP-resistant GC cells than that of the DDP-sensitive GC cells, and the activation of AKT could attenuate ZJW-induced sensitivity to DDP. These data revealed that ZJW can increase the chemosensitivity in DDP-resistant primary GC cells by inducing mitochondrial apoptosis and AKT inactivation. The combining chemotherapy with ZJW may be an effective therapeutic strategy for GC chemoresistance patients.

关键词： Primary GC cells ZJW AKT Chemoresistance

Microwave Solvothermal Synthesis, Crystal Structures and in Vitro Antitumor Activities of Di-n-butyltin Piperonylate with a Sn4O4 Ladder Framework

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Chinese Journal of Structural Chemistry 2018年第8期37卷 1265-1271页

作者：邝代治冯泳兰蒋伍玖朱小明庾江喜张复兴 Key laboratory of Functional Metal-organic Compounds of Hunan Province Key Laboratory of Functional Organometallic Materials of Hengyang Normal UniversityCollege of Hunan ProvinceCollege of Chemistry and Material ScienceHengyang Normal University

A two-dimensional supramolecular compound di-n-butyltin piperonylate, {（μ3-O）（μ2-OMe）（n-Bu2Sn）2[O2CAr（C2H4O）]}2 constructed by hydrogen bonds with a Sn4O4 ladder-like framework, was obtained by the microwave-assisted solvothermal reaction of di-n-butyltin oxide precursor with the piperonylic acid in methanol environments. The composite was characterized by elemental analysis and IR（~1H, ^（13）C and ^（119）Sn） NMR spectra. The compound crystallizes in monoclinic system, space group P21/n with a = 13.3690（12）, b = 14.1442（14）, c = 16.4022（16） A, β = 107.191（6）°, V = 2963.0（5） A^3, Z = 2, Dc = 1.520 g/cm^3, F（000） = 1368, μ = 1.719 mm^（-1）, Mo Kα radiation（λ = 0.71073 A）, the final R = 0.0495 and w R = 0.1260 for 6780 observed reflections with I 〉 2σ（I）. Its X-ray crystallography diffraction analyses show a Sn4O4 ladder-like skeleton, in which two endocyclic tin and one exo tin atoms are bonded to the μ3-O atom. In addition, one endocyclic tin and one exo tin atoms are respectively bonded to the μ2-O atom from methanol. The ladder-like molecule has a three-ring fused skeleton, which is almost coplanar. The endocyclic and exocyclic tin atoms were all five-coordinated with distorted trigonal bipyramidal geometry. The antitumor activity showed that the compound had higher activities than cisplatin in HT-29, HepG2, MCF-7, KB and A549 cell line in vitro.

关键词： di-n-butyltin piperonylate microwave solvothermal synthesis ladder-likeframework in vitro antitumor activity

Alteration of membrane lipid biophysical properties and resistance of human lung adenocarcinoma A_(549) cells to cisplatin

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Science China(Life Sciences) 2001年第1期44卷 25-32页

作者：梁兴杰黄有国 State key laboratory of Biomacromolecules Institute of Biophysics Chinese Academy of Sciences Beijing China

Alterations of membrane lipid biophysical properties of sensitiveA549 and resistant A549/DDP cells to the Cis-dichlorodiammine platinum (cisplatin) were performed by measurements of fluorescence and flow cytometry approaches using fluorescence dyes of DPH, N-AS and Merocyanine 540 (MC 540) respectively. Fatty acids of membrane lipid of the two cell lines were analyzed by gas chromatography. The results indicated clearly that fluorescence polarization (P) of the DPH probe is 0.169 for the sensitive A549 cell and 0.194 for the resistant A549/DDP cells. Statistical analysis showed significant difference between the two cell lines. The polarizations of 2-AS and 7-AS which reflect the fluidity of surface and middle of lipid bilayer are 0.134 and 0.144 for the sensitive A549 cells as well as 0.171 and 0.178 for the resistant A549/DDP cells respectively, but there is no significant difference of the polarization of 12-AS between the two cell lines. This shows that altera-tions of the membrane fluidity of both cells were mainly located on the surface and middle of the lipid bilayer. In addition, the packing density of phospholipid molecules in the membrane of the two cell lines detected by MC540 probe indicated that lipid packing of A549 cell membranes was looser than that of the A549/DDP cells. And unsaturation degree of plasma membrane fatty acids of the A549/DDP cells was also lower than that of A549 cells. Taken together, it was proposed that the al-teration of membrane lipid biophysical state may be involved in the resistance of A549/DDP cells to cisplatin.

关键词： multidrug resistance DPH MC540 N-AS probes lipid ordering fatty acids unsaturation.

Low doses of ethanolic extract of Boldo(Peumus boldus) can ameliorate toxicity generated by cisplatin in normal liver cells of mice in vivo and in WRL-68 cells in vitro, but not in cancer cells in vivo or in vitro

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Journal of Integrative Medicine 2014年第5期12卷 425-438页

作者： Jesmin Mondal Kausik Bishayee Ashis Kumar Panigrahi Anisur Rahman Khuda-Bukhsh Cytogenetics and Molecular Biology laboratory Department of Zoology University of Kalyani Fisheries and Aquaculture laboratory Department of Zoology University of Kalyani

OBJECTIVE： Use of cisplatin, a conventional anticancer drug, is restricted because it generates strong hepatotoxicity by accumulating in liver. Therefore its anticancer potential can only be fully exploited if its own toxicity is considerably reduced. Towards this goal, ethanolic extract of the plant, Boldo （Peumus boldus）, known for its antihepatotoxic effects, was used simultaneously with cisplatin, to test its ability to reduce cisplatin＇s cytotoxicity without affecting its anticancer potential. METHODS： The cytotoxicity of Boldo extract （BE） and cisplatin, administered alone and in combination, was determined in three cancer cell lines （A549, HeLa, and HepG2） and in normal liver cells （WRL-68）. Drug-DNA interaction, DNA damage, cell cycle, apoptosis, reactive oxygen species （ROS） and mitochondrial membrane potential （MMP, Aψ） were also studied. Hepatotoxicity and antioxidant activity levels were determined by alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase and glutathione assays in mice. The cytotoxicity of related proteins was tested by Western blotting. RESULTS： Co-administration of BE and cisplatin increased viability of normal cells, but had no effect on the viability of cancer cells. Boldo protected liver from damage and normalized different antioxidant enzyme levels in vivo and also reduced ROS and re-polarized MMP in vitro. Bax and cytochrome c translocation was reduced with caspase 3 down-regulation. Further, a drug- DNA interaction study revealed that BE reduced cisplatin＇s DNA-binding capacity, resulting in a reduction in DNA damage. CONCLUSION： Results indicated that a low dose of BE could be used beneficially in combination with cisplatin to reduce its toxicity without hampering cisplatin＇s anticancer effect. These findings siqnify a potential future use of BE in cancer therapy.

关键词： drug-related toxicity Peumus boldus plant ethanolic extract cytotoxicity liver anti-oxidant