奥沙利铂治疗后残余肝癌在裸鼠模型中具有增加的转移潜能，而松友饮可减弱其转移潜能。

BACKGROUND

The opposite effects of chemotherapy, which enhance the malignancy of treated cancers such as hepatocellular carcinoma (HCC), are not well understood. We investigated this phenomenon and corresponding mechanisms to develop a novel approach for improving chemotherapy efficacy in HCC.

METHODS

Human hepatocellular carcinoma cell lines HepG2 (with low metastatic potential) and MHCC97L (with moderate metastatic potential) were used for the in vitro study. An orthotopic nude mouse model of human HCC was developed using MHCC97L cells. We then assessed the metastatic potential of surviving tumor cells after in vitro and in vivo oxaliplatin treatment. The molecular changes in surviving tumor cells were evaluated by western blot, immunofluorescence, and immunohistochemistry. The Chinese herbal extract Songyou Yin (composed of five herbs) was investigated in vivo to explore its effect on the metastatic potential of oxaliplatin-treated cancer cells.

RESULTS

MHCC97L and HepG2 cells surviving oxaliplatin treatment showed enhanced migration and invasion in vitro. Residual HCC after in vivo oxaliplatin treatment demonstrated significantly increased metastasis to the lung (10/12 vs. 3/12) when re-inoculated into the livers of new recipient nude mice. Molecular changes consistent with epithelial-mesenchymal transition (EMT) were observed in oxaliplatin-treated tumor tissues and verified by in vitro experiments. The Chinese herbal extract Songyou Yin (4.2 and 8.4 g/kg) attenuated EMT and inhibited the enhanced metastatic potential of residual HCC in nude mice (6/15 vs. 13/15 and 3/15 vs. 13/15, respectively).

CONCLUSIONS

The surviving HCC after oxaliplatin treatment underwent EMT and demonstrated increased metastatic potential. Attenuation of EMT by Songyou Yin may improve the efficacy of chemotherapy in HCC.

背景

化疗的相反作用，即增强已治疗癌症（如肝细胞癌[HCC]）的恶性程度，尚未得到很好的理解。我们研究了这一现象及其相应的机制，以开发一种提高 HCC 化疗疗效的新方法。

方法

使用人肝癌细胞系 HepG2（转移潜能低）和 MHCC97L（转移潜能中等）进行体外研究。使用 MHCC97L 细胞建立人 HCC 原位裸鼠模型。然后评估体外和体内奥沙利铂治疗后存活肿瘤细胞的转移潜能。通过 Western blot、免疫荧光和免疫组化评估存活肿瘤细胞的分子变化。体内研究了中药提取物“松友饮”（由五种草药组成），以探讨其对奥沙利铂处理的癌细胞转移潜能的影响。

结果

奥沙利铂处理后存活的 MHCC97L 和 HepG2 细胞在体外表现出增强的迁移和侵袭能力。重新接种到新受体裸鼠肝脏中的体内奥沙利铂治疗后残留的 HCC 明显增加了向肺部的转移（10/12 对 3/12）。在奥沙利铂处理的肿瘤组织中观察到与上皮间质转化（EMT）一致的分子变化，并通过体外实验得到验证。中药提取物“松友饮”（4.2 和 8.4 g/kg）减弱了 EMT，并抑制了裸鼠中残留 HCC 增强的转移潜能（分别为 6/15 对 13/15 和 3/15 对 13/15）。