[Effects of paclitaxel and gefitinib on the proliferation and cell cycle of human lung adenocarcinoma cell SPC-A1.].
BACKGROUND
Previous clinical trials showed that there was no clinical benefit in the treatment of advanced non-small cell lung cancer when chemotherapy combined with gefitinib. The present study aims to assess the sequential administration of paclitaxel and gefitinib on the cell proliferation of lung adenocarcinoma cell SPC-A1 and to explore its mechanism by observing their effects on the cell cycle.


METHODS
The expression of EGFR mRNA and EGFR protein were examined by RT-PCR and western blotting respectively. MTT was used to measure the cell proliferation of SPC-A1 cells. Cell cycle was detected by flow cytometry.


RESULTS
Both EGFR mRNA and EGFR protein were overexpressed in SPC-A1 cells. From 1*10(-14) M to 1*10(-6) M, both paclitaxel and gefitinib inhibited the cell proliferation of SPC-A1 cells in a dose-dependent and time-dependent manner in vitro . The effects of paclitaxel in combination with gefitinib on cell proliferation depended on the sequence. No significant additive effects on cell proliferation was found when they were used simultaneously or gefitinib was added before paclitaxel. However, sequential administration of gefitinib following paclitaxel can remarkably enhanced the effect of paclitaxel on the cell proliferation of SPC-A1 cells. Cell cycle studies showed that paclitaxel and gefitinib induced G2/M and G0/G1 arrest respectively. The G0/G1 arrest was observed when paclitaxel and gefitinib was used simultaneously or gefitinib was added before paclitaxel. In contrast, sequential administration of gefitinib following paclitaxel induced G2/M arrest.


CONCLUSIONS
Both paclitaxel and gefitinib inhibits the cell proliferation of SPC-A1 cells. The additive effects on cell proliferation are sequential-dependent. The concomitant and the sequential treatment of gefitinib followed by paclitaxel exert no significant additive effects on the cell proliferation and resulted in the accumulation of cells in G0/G1 phase, which may decrease the effectiveness of paclitaxel in subsequent cycles. The additive effected on the cell proliferation are observed only when gefitinib is sequentially administrated following paclitaxel, which results in the G2/M arrest. The increase in G2/M phase suggests that cell cycle effects might not explain the observed additive effects.
Jia
Gang
G
Department of Medical Oncology, Guangzhou General Hospital of Guangzhou Military Command, Guangzhou, Guangdong 510010, China; Graduate School, Guangzhou Medical Institution, Guangzhou, Guangdong 510182, China.
Zhang
Weimin
W
Zhou
Juan
J
Zhu
Zhixia
Z