The Synergistic Radiosensitization Of Paclitaxel And Gemcitabine On Nasopharyngcal Carcinoma Cell Line HNE₂

Objective To observe the synergistic radiosensitization of paclitaxel(PA) and gemcitabine(GE) on nasopharyngcal carcinoma(NPC) cell line HNE2, and discuss the mechanism of it.Methods IC50 and IC10 of GE and PA were calculated by MTT. Irradiation(6Gy) during GE and/or PA exposure,immediately after GE and/or PA exposure or 4,8,24,48 hours after GE and/or PA exposure,the Inhibition ratio of cell was evaluated. Cytotoxicity was measured by exposing HNE2 cells to GE and/or PA simultaneously or individually, followed by irradiation at 6 Gy. The Sensitizing Enhancement Ratio ( SER ) was evaluated by clonogenic assay. Cell cycle distribution and apoptosis was assessed by flow cytometry. Western Blot was used to measure the expression of bcl-2 and bax.Results The IC50 and IC10 of GE was 173.2μg/ml和0.210μg/ml;The IC50 and IC10 of PA was 2.73μg/ml和0.13μg/ml. MTT showed that the Inhibition ratio of cell depend on the exposure to GE and/or PA simultaneously or individually, and 48h exposure showed better effect. The SER of GE, PA and both drugs was 1.06, 1.13 and 1.34 respectivety. A 96.03% S phase block and 31.62% apoptosis were observed after treatment with GE, while a 75.71% G2/M phase block and 44.56% apoptosis were observed after treatment with PA. When both drugs were used in combination, the ratio of G2/M phase arrest induced by PA was changed from 75.71% to 65.98%, the ratio of S phase block was increased to 33.33%,and a higher apoptosis was observed(73.28%). Western blot assay showed that GE and PA both increased the level of Bax expression and inhibited the level of bcl-2 expression. When used in combination, they further increased the level of Bax expression and inhibited the level of bcl-2 expression.Conclusion1,PA and GE can both enhanced radiosensitization in HNE2 cells. the radiosensitization depend on the exposure to GE and/or PA simultaneously or individually, and 48h exposure showed better effect.2,When used together, they can further enhanced radiosensitization in HNE2 cells. It show great potential in the treatment of NPC.3,The radiosensitizing effects of both drugs seem to be related to enhanced apoptosis and control the expression of bcl-2 and bax. .