TY - JOUR
AB - Cisplatin resistance is an obstacle for the effective treatment of non‑small cell lung cancer (NSCLC). The combined use of two or more chemotherapeutic agents displays advantages for the clinical treatment of drug‑resistant lung cancer. The present study aimed to assess the synergy of the dual PI3K/Akt/mTOR signaling pathway inhibitor NVP‑BEZ235 and cisplatin, a chemotherapeutic agent, on proliferation, apoptosis, cell cycle arrest and protein expression in cisplatin‑resistant NSCLC A549/diamminedichloroplatinum resistance (DDP) cells. Cell proliferation was determined by performing Cell Counting Kit 8 and colony formation assays. Combination index (CI) was used to assess the combinatorial effects of NVP‑BEZ235 and cisplatin. Cellular apoptosis and cell cycle arrest were detected via flow cytometry. Western blotting was performed to evaluate protein expression levels relative to β‑actin. Cisplatin and NVP‑BEZ235 displayed the strongest synergy (CI50=0.23) at the mass ratio of 10:1. The half inhibitory concentrations of cisplatin and NVP‑BEZ235 at 10:1 were 1.53 and 0.15 µg/ml, respectively. Compared with the control group, the combination of cisplatin and NVP‑BEZ235 induced cell apoptosis and inhibited colony formation. Furthermore, compared with the control group, phosphorylation of Akt and p70S6 Kinase was significantly inhibited and cell cycle was arrested at G0G1 phase in the combination treatment group. The expression levels of drug efflux proteins, such as multidrug resistance‑associated protein 1 and ATP‑binding cassette sub‑family G member 2, were significantly decreased when A549/DDP cells were treated with a combination of cisplatin and NVP‑BEZ235 compared with the control group. Collectively, the present study indicated that the combined treatment of cisplatin and NVP‑BEZ235 displayed synergistic antitumor effects on drug‑resistant A549/DDP cells, by which the antiproliferative effects may occur via inhibition of the PI3K/Akt/mTOR signaling pathway and downregulation of drug efflux.
AD - Department of Pharmacy, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, P.R. China
AU - Zhu,Hao
AU - Shi,Yuhuan
AU - Jiao,Xiuxiu
AU - Yang,Gang
AU - Wang,Rong
AU - Yuan,Yongfang
DA - 2020/12/01
DO - 10.3892/ol.2020.12189
IS - 6
JO - Oncol Lett
KW - drug resistance
non‑small cell lung cancer
cisplatin
NVP‑BEZ235
combination therapy
PY - 2020
SN - 1792-1074
1792-1082
SP - 326
ST - Synergistic antitumor effect of dual PI3K and mTOR inhibitor NVP‑BEZ235 in combination with cisplatin on drug‑resistant non‑small cell lung cancer cell
T2 - Oncology Letters
TI - Synergistic antitumor effect of dual PI3K and mTOR inhibitor NVP‑BEZ235 in combination with cisplatin on drug‑resistant non‑small cell lung cancer cell
UR - https://doi.org/10.3892/ol.2020.12189
VL - 20
ER -