Effect of Guizhi Fuling Capsule on Apoptosis of Myeloma Cells Through Mitochondrial Apoptosis Pathway

作     者：SUN Run-jie XU Jie GAO Wei ZHANG Yan-yu SUN Xiao-qi JI Lin CUI Xing SUN Run-jie;XU Jie;GAO Wei;ZHANG Yan-yu;SUN Xiao-qi;JI Lin;CUI Xing

作者机构：Department of Traditional Chinese MedicineShandong University of Traditional Chinese MedicineJinan 250014China Department of HematologyAffiliated Hospital of Shandong University of Traditional Chinese MedicineJinan 250014China Department of LaboratoryAffiliated Hospital of Shandong University of Traditional Chinese MedicineJinan 250014China Department of Neurologythe Second Affliated Hospital of Shandong University of Traditional Chinese MedicineJinan 250001China Department of Oncologythe Second Affiliated Hospital of Shandong University of Traditional Chinese MedicineJinan 250001China 

出 版 物：《Chinese Journal of Integrative Medicine》 (中国结合医学杂志（英文版）)

年 卷 期：2023年第29卷第2期

页      面：127-136页

核心收录：

学科分类：1006[医学-中西医结合] 1002[医学-临床医学] 10[医学] 100602[医学-中西医结合临床] 

基　　金：Supported by the National Natural Science Foundation of China(No.82074348) the Taishan Scholar Project(No.tsqn201812145) the Key Technology Research and Development Program of Shandong(No.2019GSF108162) the Natural Science Foundation of Shandong Province(No.ZR2020MH388)。 

主　　题：Guizhi Fuling Capsule mitochondrial apoptosis multiple myeloma 

摘      要：Objective: To observe the effects of Guizhi Fuling Capsule(GZFLC) on myeloma cells and explore the mechanisms. Methods: MM1S and RPMI 8226 cells were co-cultured with different concentrations of serum and the cell experiments were divided into negative(10%, 20% and 40%) groups, GZFLC(10%, 20%, and 40%)groups and a control group. Cell counting kit-8(CCK-8) assays and flow cytometry were used to detect the viability and apoptosis levels of myeloma cells. The effects on mitochondria were examined by reactive oxygen specie(ROS) and tetrechloro-tetraethylbenzimidazol carbocyanine iodide(JC-1) assays. Western blot was used to detect the expression of B cell lymphoma-2(Bcl-2), Bcl-2-associated X(Bax), cleaved caspase-3,-9, cytochrome C(Cytc)and apoptotic protease-activating factor 1(Apaf-1). RPMI 8226 cells(2×107) were subcutaneously inoculated into 48 nude mice to study the in vivo antitumor effects of GZFLC. The mice were randomly divided into four groups using a completely randomized design, the high-, medium-, or low-dose GZFLC(840, 420, or 210 mg/kg per day,respectively) or an equal volume of distilled water, administered daily for 15 days. The tumor volume changes in and survival times of the mice in the GZFLC-administered groups and a control group were observed. Cytc and Apaf-1 expression levels were detected by immunohistochemistry. Results: GZFLC drug serum decreased the viability and increased the apoptosis of myeloam cells(P0.05). In addition, this drug increased the ROS levels and decreased the mitochondrial membrane potential(P0.01). Western blot showed that the Bcl-2/Bax ratios were decreased in the GZFLC drug serum-treated groups, whereas the expression levels of cleaved caspase-3,-9,Cytc and Apaf-1 were increased(all P0.01). Over time, the myeloma tumor volumes of the mice in the GZFLCadministered groups decreased, and survival time of the mice in the GZFLC-administered groups were longer than that of the mice in the control group. Immunohistochemical analysis of tumor tissues from the mice in the GZFLCadministered groups revealed that the Cytc and Apaf-1 expression levels were increased(P0.05). Conclusion:GZFLC promoted apoptosis of myeloma cells through the mitochondrial apoptosis pathway and significantly reduced the tumor volumes in mice with myeloma, which prolonged the survival times of the mice.