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- 2018
血红素加氧酶-1在胃癌顺铂化疗敏感性中的作用
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Abstract:
摘要：目的 研究血红素加氧酶-1(HO-1)及其抑制剂在胃癌顺铂(CDDP)化疗中的作用，为胃癌化疗敏感性提供潜在的增敏靶点。方法 MTT法检测锌原卟啉IX (ZnPPIX)及CDDP对胃癌细胞株SGC7901增殖能力的影响；Western blot和Real-time PCR分别检测胃癌细胞中HO-1蛋白和mRNA的表达；构建裸鼠皮下种植瘤模型并进一步观察ZnPPIX及CDDP对胃癌成瘤能力的影响。结果 CDDP联合ZnPPIX干预胃癌细胞明显抑制肿瘤细胞的增殖率(P<0.05)；同时，CDDP胃癌细胞中HO-1 mRNA水平和蛋白的表达增加(P<0.05)。而CDDP联合ZnPPIX干预细胞组的HO-1的表达较对照组明显降低(P<0.05)。荷瘤实验结果显示，CDDP可抑制胃癌皮下种植瘤的生长，肿瘤体积和质量明显降低。结论 HO-1抑制剂ZnPPIX可增强CDDP对胃癌的化疗敏感性，有可能成为潜在的胃癌CDDP化疗方案的增敏剂。
ABSTRACT: Objective To explore the roles of heme oxygenase-1 (HO-1) and protoporphyrin zinc IX (ZnPPIX), its inhibitor, in cisplatin chemotherapy for gastric cancer so as to provide potential targets for chemosensitivity in gastric cancer. Methods Gastric cancer cell line SGC7901 was used in vitro. MTT assay was carried out to determine the effects of ZnPPIX and CDDP on the proliferation in gastric cancer cells. The expression of HO-1 in gastric cancer cells was measured by Real-time PCR and Western blot, respectively. The gastric cancer xenografts in nude mice were used to study the effects of ZnPPIX and CDDP in gastric cancer on tumor formation in vivo. Results The proliferation of cancer cells, interfered by CDDP in combination with ZnPPIX, could be significantly inhibited (P<0.05). Moreover, CDDP could increase the expression of HO-1 in gastric cancer cells, which was reversed by ZnPPIX (P<0.05). The animal experiment showed that CDDP could inhibit gastric cancer growth in nude mice and reduce tumor volume and weight. Conclusion ZnPPIX could enhance the chemosensitivity of CDDP in gastric cancer, which may be a potential sensitizer of cisplatin-based chemotherapy in gastric cancer
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