Abstract：
HCC is the most common fatal malignancy. Although surgical resection is the primary treatment strategy, most patients are not eligible for resection due to tumor heterogeneity, underlying liver disease, or comorbidities. Therefore, this study explores the possibility of multi-molecular targeted drug delivery in treating HCC. In this study, we constructed the recombinant adenovirus co-expressing apoptin and melittin (MEL) genes. The inhibitory effect of the recombinant adenovirus on hepatocellular carcinoma cells was detected through experiments on cell apoptosis, migration, invasion, and other factors. The tumor inhibitory effect in vivo was assessed using subcutaneous HCC mice. Results showed that recombinant adenovirus co-expressing anti-tumor genes TAT and apoptin, RGD and MEL can significantly inhibit the proliferation, migration, and invasion of HCC cells by inducing an increase in reactive oxygen species (ROS) levels, upregulation of apoptotic proteins such as Bax, cleaved caspase-3, and cleaved caspase-9, and downregulation of the anti-apoptotic protein Bcl-2. In subcutaneous HCC mice, recombinant adenovirus induced significant apoptosis in tumor, and inhibited tumor growth. In conclusion, recombinant adenovirus co-expressing apoptin and MEL can inhibit the growth and proliferation of tumor cells both in vivo and in vitro.
摘要：
HCC是最常见的致命恶性肿瘤。虽然手术切除是主要的治疗策略，由于肿瘤异质性，大多数患者不符合切除条件，潜在的肝脏疾病，或合并症。因此,本研究探讨了多分子靶向给药治疗HCC的可能性。在这项研究中,我们构建了共表达凋亡素和蜂毒素（MEL）基因的重组腺病毒。通过细胞凋亡实验检测重组腺病毒对肝癌细胞的抑制作用,迁移,入侵,和其他因素。使用皮下HCC小鼠评估体内肿瘤抑制作用。结果表明，共表达抗肿瘤基因TAT和凋亡素的重组腺病毒，RGD和MEL能显著抑制其增殖，迁移,通过诱导活性氧（ROS）水平的增加和肝癌细胞的侵袭，凋亡蛋白如Bax的上调，裂解的caspase-3和裂解的caspase-9，以及抗凋亡蛋白Bcl-2的下调。在皮下肝癌小鼠中，重组腺病毒诱导肿瘤细胞凋亡,并抑制肿瘤生长。总之,共表达凋亡素和MEL的重组腺病毒可以在体内和体外抑制肿瘤细胞的生长和增殖。
