机构：[1]Department of Oncology, Clinical and Basic Research Team of TCM Preventionand Treatment of NSCLC, Guangdong Provincial Hospital of Chinese Medicine,The Second Clinical Medical College of Guangzhou University of ChineseMedicine, No .111, Dade Road, Guangzhou 510120, Guangdong, People’sRepublic of China大德路总院肿瘤科广东省中医院[2]The Postdoctoral Research Station, Guangdong ProvincialHospital of Chinese Medicine, Guangzhou University of Chinese Medicine,Guangzhou 510120, Guangdong, People’s Republic of China[3]The Basic MedicineCollege, Guangzhou University of Chinese Medicine, Guangzhou 510002,Guangdong, People’s Republic of China[4]School of Nursing, GuangzhouKangda Vocational Technical College, Guangzhou 511363, Guangdong,People’s Republic of China[5]Guangdong Provincial Key Laboratory of ClinicalResearch on Traditional Chinese Medicine Syndrome, Guangzhou 510120,Guangdong, People’s Republic of China
BackgroundOur previous clinical study has shown that Chinese herbal medicine (CHM) Fuzheng Kang-Ai (FZKA) decoction is effective in treating advanced lung cancer patients through prolonging the drug resistance to Gefitinib (GFTN). Our basic study found that FZKA decoction could enhance the inhibition effect of GFTN in lung cancer by inactivating PI3K/Akt pathway. Moreover, our recent work showed that FZKA induced lung cancer cell apoptosis via STAT3/Bcl-2/Caspase-3 pathway. Thus in this study, we aim to elucidate how FZKA enhances the effect of GFTN in lung cancer from the perspective of cell apoptosis.MethodsCell proliferation and colony formation assay were performed to detect the cell growth inhibition. Flow cytometry and TUNEL assay were carried out to test the cell apoptosis. Mitochondrial membrane potential (MMP) assay was done to measure the alteration of MMP. Caspase-3/-9 activity assay was used to test the activity of caspase-3/-9. Western blot and qRT-PCR were done to detect the expression of STAT3 and Bcl-2 family as well as Caspase-3/-9 and Cyt-C at protein and mRNA levels, respectively. Transient transfection was performed to silence STAT3 using siSTAT3. Animal model was done to validate the molecular mechanisms in vivo and immunohistochemistry was done to detect the expression of Bax and Caspase-3.ResultsFirstly, our results showed that FZKA enhanced the inhibition effect of GFTN in lung cancer both in vitro and in vivo. Secondly, cell apoptosis was enhanced when treating lung cancer cells with both FZKA and GFTN, a process involving the mitochondria and the Bcl-2 family. And Bcl-2 family was involved in this process. Interestingly, STAT3 plays a critical role on mediating the above process. Last but not the least, the enhanced effect of cell apoptosis induction of GFTN by FZKA was validated in animal model.ConclusionOur findings conclude that Fuzheng Kang-Ai decoction enhances the effect of GFTN-induced cell apoptosis in lung cancer through the mitochondrial pathway, providing a novel molecular mechanism by which FZKA sensitizes to GFTN by delaying drug resistance in treating lung cancer patients.
基金：
Guangdong Natural Science Foundation of ChinaNational Natural Science Foundation of Guangdong Province [2017A030310326, 2019A1515011362]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China [81903991, 81974543]; Guangzhou science and technology plan project [201804010149, 202002030155]; China Postdoctoral Science Foundation ProjectChina Postdoctoral Science Foundation [2018M630941]; Major Research Projects in First-class Disciplines of Guangzhou University of Chinese Medicine [A1260619111001]; Guangdong science and technology plan project [2016A020215134]; Chinese medicine science and technology research project of Guangdong Provincial Hospital of Chinese Medicine [YN2019MJ09, YN2016QJ03, YN2019QJ06]; Guangdong medical science and Technology Research Foundation [A2018251]; Science and Technology Planning Project of Guangdong Province [2017B030314166]
第一作者机构：[1]Department of Oncology, Clinical and Basic Research Team of TCM Preventionand Treatment of NSCLC, Guangdong Provincial Hospital of Chinese Medicine,The Second Clinical Medical College of Guangzhou University of ChineseMedicine, No .111, Dade Road, Guangzhou 510120, Guangdong, People’sRepublic of China[2]The Postdoctoral Research Station, Guangdong ProvincialHospital of Chinese Medicine, Guangzhou University of Chinese Medicine,Guangzhou 510120, Guangdong, People’s Republic of China[5]Guangdong Provincial Key Laboratory of ClinicalResearch on Traditional Chinese Medicine Syndrome, Guangzhou 510120,Guangdong, People’s Republic of China
通讯作者：
通讯机构：[1]Department of Oncology, Clinical and Basic Research Team of TCM Preventionand Treatment of NSCLC, Guangdong Provincial Hospital of Chinese Medicine,The Second Clinical Medical College of Guangzhou University of ChineseMedicine, No .111, Dade Road, Guangzhou 510120, Guangdong, People’sRepublic of China[2]The Postdoctoral Research Station, Guangdong ProvincialHospital of Chinese Medicine, Guangzhou University of Chinese Medicine,Guangzhou 510120, Guangdong, People’s Republic of China[5]Guangdong Provincial Key Laboratory of ClinicalResearch on Traditional Chinese Medicine Syndrome, Guangzhou 510120,Guangdong, People’s Republic of China
推荐引用方式(GB/T 7714)：
Wang Sumei,Peng Zhiwei,Li Wenjuan,et al.Fuzheng Kang-Ai decoction enhances the effect of Gefitinib-induced cell apoptosis in lung cancer through mitochondrial pathway[J].CANCER CELL INTERNATIONAL.2020,20(1):doi:10.1186/s12935-020-01270-3.
APA：
Wang, Sumei,Peng, Zhiwei,Li, Wenjuan,Long, Shunqin,Xiao, Shujing&Wu, Wanyin.(2020).Fuzheng Kang-Ai decoction enhances the effect of Gefitinib-induced cell apoptosis in lung cancer through mitochondrial pathway.CANCER CELL INTERNATIONAL,20,(1)
MLA：
Wang, Sumei,et al."Fuzheng Kang-Ai decoction enhances the effect of Gefitinib-induced cell apoptosis in lung cancer through mitochondrial pathway".CANCER CELL INTERNATIONAL 20..1(2020)
