Kanglaite reverses multidrug resistance of HCC by inducing apoptosis and cell cycle arrest via PI3K/AKT pathway
Authors Yang C, Hou A, Yu C, Dai L, Wang W, Zhang K, Shao H, Ma J, Xu W
Received 11 October 2017
Accepted for publication 13 December 2017
Published 26 February 2018 Volume 2018:11 Pages 983—996
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Akshita Wason
Peer reviewer comments 4
Editor who approved publication: Dr Ingrid Espinoza
Chendong Yang,1,* Aihua Hou,1,2,* Chunfeng Yu,1 Lingling Dai,1 Wen Wang,1 Kangle Zhang,1 Hongmin Shao,1 Jinghua Ma,1 Wenjuan Xu2
1Yantai Hospital of Traditional Chinese Medicine, 2Binzhou Medical University, Yantai, China
*These authors contributed equally to this work
Background: Multidrug resistance (MDR) frequently contributes to the failure of chemotherapeutic treatments in patients diagnosed with hepatocellular carcinoma (HCC). Revealing the molecular mechanism of MDR is indispensable for the development of effective chemotherapeutic drugs.
Purpose: Due to the low-toxicity modulators to inhibit MDR, we considered that Kanglaite (KLT) is a potential agent for reversing MDR in HCC.
Materials and Methods: BEL-7402/5-fluorouracil (5-FU) and HepG2/adriamycin (ADM) were analyzed for cell viability, colony formation assay, cell scratch assay, and cell cycle analysis and apoptosis assay by flow cytometry. The expression of PARP, caspase-3, Bax, Bcl-2, CDC25C, Cyclin B1 and phosphorylation of PTEN, PI3K, and AKT in HepG2/ADM cells were detected by western blotting.
Results: The proliferation of drug-resistant cell lines BEL-7402/5-FU and HepG2/ADM pretreated with KLT was significantly inhibited when compared with drug alone. KLT could increase the accumulation of ADM in HepG2/ADM cells. In this study, we found that KLT treatment notably reduced cell viability, induced apoptosis and cell cycle arrest in human HepG2/ADM and BEL-7402/5-FU cells, and effectively reversed the MDR by p-glycoprotein (P-gp) inhibition. Moreover, KLT decreased the phosphorylation of AKT and PI3K in KLT-treated HepG2/ADM cells. These data together implied that KLT might reverse drug resistance in HCC by blocking the PI3K/AKT signaling.
Conclusion: We demonstrated that KLT reversed MDR of human HCC by inducing apoptosis and cell cycle arrest via the PI3K/AKT signaling pathway.
Keywords: kanglaite, multidrug resistance, hepatocellular carcinoma, apoptosis, PI3K/AKT pathway
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