三氧化二砷联合奥沙利铂对肝癌细胞增殖及凋亡的影响

Study on the proliferation and apoptosis by combining arsenic trioxide with oxaliplatin in HepG2 Cells in vitro

目的:探讨三氧化二砷(As2O3)、奥沙利铂(L-OHP)协同抑制人肝癌细胞株HepG2细胞增殖及诱导凋亡的作用。方法:采用MTT法检测As2O3、L-OHP单药或联合对HepG2细胞的生长抑制作用;以AnnexinV/PI双染色流式细胞术检测As2O3、L-OHP单药或联合对HepG2细胞凋亡的影响。结果:不同浓度的As2O3、L-OHP单药或联合均可显著抑制HepG2细胞的生长,抑制作用在一定范围内呈浓度依赖性及时间依赖性,两药联合抑制作用明显增强(P<0.05)。0.5,2.0,4.0mg.L-1的As2O3及2.5,5.0mg.L-1的L-OHP所诱导的早期凋亡细胞较对照组明显增多(P<0.01),0.5mg.L-1的As2O3与2.5mg.L-1的L-OHP联合作用可使HepG2细胞早期凋亡细胞明显增多(P<0.01);随着联合浓度增加,晚期凋亡及坏死细胞明显增多(P<0.01)。结论:As2O3及L-OHP均可有效地抑制体外肝癌HepG2细胞的生长并诱导细胞凋亡,两药联合具有协同抑制细胞增殖及诱导凋亡作用。

OBJECTIVE To explore the synergistic effect of arsenic trioxide （As2O3） and Oxaliplatin （L-OHP） on the inhibition of proliferation and the induction of apoptosis in human Hepatocarcinoma HepG2 Cell lines in vitro. METHODS HepG2 cells were treated with As2O3 or L-OHP alone,and were treated with As2O3 in combination with L-OHP. The inhibition of proliferation was determined by MTT, and the apoptosis rate was assessed by AnnexinV/P1 staining. RESULTS As203andL- OHP at different concentrations could obviously inhibit the growth of HepG2 cell lines. Growth inhibition of HepG2 cell strongly depended on the concentration and the treatment time of As2O3 or oxaliplatin. With As2O3 at the dosage of 0. 25-4.0 mg·L^-1,L-OHP at the dosage of 2. 5-40. 0 mg·L^-1, the combination of As2O3 and L-OHP effectively enhanced the growth inhibition,compared to separate use of either alone（P〈0. 05）. As, O3 and LOHP at different concentrations could obviously induce apoptosis of HepG2 cell lines. The early apoptosis in HepG2 cell line under 0. 5, 2. 0, 4. 0 mg·L^-1 of As2O3or 2. 5, 5. 0 mg·L^-1 of LOHP is more significant than control group （P〈0. 01）. Combination of 0. 5 mg·L^-1 As2O3. with 2. 5 mg·L ·L^-1 OHP led to much higher apoptotic rates, as compared with the either drug used alone（P〈0. 01 ）. CONCLUSION As2O3 and L- OHP could inhibit proliferation and induce apoptosis of HepG2 Cells in vitro. , and two drugs could produce a significant synergic effect.