美洲大蠊提取物对肝癌皮下移植瘤裸鼠自噬和侵袭转移的影响

Effects of Periplaneta americana Extract on Autophagy and Invasive Metastasis of Subcutaneous Transplanted Hepatocellular Carcinoma in Nude Mice

目的 研究美洲大蠊提取物CⅡ-3和脱脂膏对肝癌耐药细胞BEL-7 402/5-FU自噬和侵袭转移的影响以及初步的作用机制。方法 对接种肝癌敏感细胞BEL-7 402和肝癌耐药细胞BEL-7 402/5-FU的移植瘤裸鼠,通过索拉菲尼、CⅡ-3和脱脂膏药物处理后,观察给药后裸鼠血清生化指标,裸鼠瘤块变化和心、肝、肾、脾等脏器指数的变化,以及肝脏和瘤块病理学改变,同时观察肿瘤组织细胞中的自噬相关因子和侵袭转移相关因子的变化。结果 CⅡ-3和脱脂膏能使裸鼠体重呈下降趋势,并抑制肿瘤的生长,明显减轻瘤重(P <0.01);CⅡ-3能提高脾脏指数和心脏指数(P <0.05);与耐药组相比,CⅡ-3组裸鼠血清CR有升高趋势(P <0.05);索拉菲尼和CⅡ-3处理组能诱导肿瘤组织坏死,作用优于脱脂膏组;与耐药组相比,除AKT外(P> 0.05),CⅡ-3和脱脂膏给药组均能明显抑制自噬和侵袭转移相关因子(P <0.05)。结论 美洲大蠊提取物CⅡ-3和脱脂膏均能抑制肝癌耐药细胞的自噬和侵袭转移,同时具有较好的抑瘤作用。其对裸鼠肝癌移植瘤的肝肾损伤有待进一步观察。

Objective To investigate the effects and preliminary mechanisms of the extract CⅡ-3 and defatted ointment of Periplaneta americana on autophagy,invasion and metastasis of drug-resistant hepatocellular carcinoma cell line BEL-7402/5-FU.Methods The transplantation tumors of liver cancer-sensitive cells BEL-7402 and liver cancer-resistant cells BEL-7402/5-FU were treated with Sorafenib,CⅡ-3,and defatted ointment drugs.Then,the serum biochemical indicators of the nude mice,changes in tumor size,and changes in organ indices such as heart,liver,kidney,and spleen were observed after drug administration.The histopathological changes in the liver and tumor were also observed,along with changes in autophagy-related factors and invasion and metastasis-related factors in tumor tissue cells.Results CⅡ-3 and the deffated cream reduced the body weight of nude mice and inhibited tumor growth,significantly reducing tumor weight(P<0.01).CⅡ-3 increased the spleen index and heart index(P<0.05);compared to the drug-resistant group,the CⅡ-3 group showed an upward trend in serum CR(P<0.05).Sorafenib and CⅡ-3 treatment induced tumor tissue necrosis,with better effects than the deffatede ointment group;compared to the drug-resistant group,both the CⅡ-3 and deffatede ointment groups significantly inhibited autophagy and invasion-related factors,except for AKT(P<0.05).Conclusion Peri-planeta americana extract CⅡ-3 and deffatede ointment can inhibit the autophagy,invasion and metastasis of drug-resistant hepatocellular carcinoma cells,and also have a good anti-tumor effect.Further observation is needed for its liver and kidney damage on nude mice with hepatocellular carcinoma transplanted tumors.