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目的:探讨胃癌组织乏氧诱导因子-1α(hypoxia-inducible factor-1α,HIF-1α)表达与P-糖蛋白(P-gp)、p53和Survivin及体外化疗敏感性的关系。方法:对63例胃癌新鲜肿瘤组织进行体外细胞培养化疗药敏性实验,标本行上述指标免疫组化染色。结果:1)胃癌组织HIF-1α、P-gp、p53和Survivin阳性表达率分别为33.3%、71.4%、50.8%和66.7%。2)肿瘤HIF-1α表达与p53表达呈正相关(r=0.407 2,P<0.01),与P-gp、Survivin表达无明显相关性(r=0.178 6、r=0.082 9,均P>0.05),其余因子之间表达均无明显相关性(r=0.163 4～0.205 4,均P>0.05)。3)10种化疗药物对4种蛋白阴、阳性表达组的肿瘤细胞平均抑制率不同。胃癌HIF-1α阳性表达组中,VCR、OPT、eADM和MTX对肿瘤细胞平均抑制率明显低于HIF-1α阴性表达组(t=2.287～3.494,均P<0.05)。VCR、PTX、eADM、CDDP和MTX对胃癌细胞抑制率降低均与2种以上蛋白的过表达有关,仅OPT、OXA的抑制率降低与一种因子阳性表达有关。结论:HIF-1α在胃癌组织中表达与部分化疗药物的耐药性有关,HIF-1α参与了肿瘤的化疗多药耐药性。
Objective: To investigate the relationship between the expression of hypoxia-inducible factor-1α (HIF-1α) and the sensitivity of P-glycoprotein (P-gp), p53 and Survivin in gastric cancer and in vitro chemosensitivity. Methods: 63 cases of fresh gastric cancer tissue cells in vitro chemosensitivity experiments, the above line immunohistochemical staining. Results: 1) The positive rates of HIF-1α, P-gp, p53 and Survivin in gastric cancer tissues were 33.3%, 71.4%, 50.8% and 66.7% respectively. There was no significant correlation between the expression of P-gp and Survivin (r = 0.178 6, r = 0.082 9, all P> 0.05) .2 There was a positive correlation between the expression of HIF- , There was no significant correlation between other factors (r = 0.163 4 ~ 0.205 4, all P> 0.05). 3) 10 kinds of chemotherapy drugs on the four kinds of protein negative, positive expression of tumor cells with different average inhibition rates. The mean inhibitory rates of VCR, OPT, eADM and MTX on tumor cells in HIF-1α-positive gastric cancer group were significantly lower than those in HIF-1α negative group (t = 2.287-3.494, all P <0.05). The inhibitory rates of VCR, PTX, eADM, CDDP and MTX on gastric cancer cells were related to the overexpression of more than two proteins. Only the inhibition rate of OPT and OXA decreased with the positive expression of one factor. Conclusion: The expression of HIF-1α in gastric cancer is related to the chemoresistance of some chemotherapeutic drugs. HIF-1α is involved in the chemoresistance of tumors.