Inhibition of proliferation and apoptosis induced by a Na+/H+ exchanger-1 (NHE-1) antisense gene on drug-resistant human small cell lung cancer cells.
The goal of this study was to evaluate the effect of the Na+/H+ exchanger-1 (NHE-1) antisense gene on drug-resistant human small cell lung cancer (SCLC) cell proliferation and apoptosis. A recombinant NHE-1 antisense gene was transfected into drug-resistant human SCLC H446/CDDP cells. Intracellular pH (pHi) was measured with fluorescence spectrophotometry. Cell proliferation was assayed cytometrically, and expression of the apoptosis gene caspase-3 was assayed using immunohistochemistry. Apoptosis and the cell cycles were imaged using a flow cytometer. pHi decreased significantly in transfected cells compared with control cells transfected with an empty vector (6.86+/-0.01 and 7.25+/-0.02, respectively, P<0.01). Cell proliferation began to decrease 48 h after antisense gene transfection, and the expression of the caspase-3 was stronger in transfected cells compared to the control group. The drug resistant exponent was significantly decreased (P<0.01), and there were more cells in G1 in the transfected group compared to the control group (70 and 57%, respectively, P<0.05). The rate of apoptosis in transfected cells was significantly higher than in the control group (12.18+/-1.86 and 2.37+/-0.33%, respectively, P<0.01). The NHE-1 antisense gene was able to induce drug-resistant human SCLC H446/CDDP cells to become acidified and apoptotic, which could provide a novel therapy for multidrug resistance SCLC.
Department of Respiratory Medicine, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, PR China.
Shujun
S
Li
Pengtao
P
Bao
Zhikui
Z
Li
Hf
H
Ouyang
Changgui
C
Wu
Guisheng
G
Qian
D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000235:genetics; D048708:Cell Growth Processes / Q000235:genetics; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000628:therapy*; D016372:RNA, Antisense / Q000235:genetics*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D055752:Small Cell Lung Carcinoma / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000628:therapy*; D017923:Sodium-Hydrogen Exchangers / Q000096:biosynthesis / Q000235:genetics*; D014162:Transfection
D000970:Antineoplastic Agents; D016372:RNA, Antisense; D012333:RNA, Messenger; D017923:Sodium-Hydrogen Exchangers