基于整合素α5β1/PI3K/AKT信号通路探讨抗纤抑癌方干预肝癌前病变的作用机制研究

Hepatic precancerous lesions is the essential stage of hepatocellular carcinoma(HCC). People may prevent HCC effectively if the pathological process of hepatic precancerous lesions can be reversed. Kangxianyiai(KXYA) decoction is an experiential prescription in our hospital for the treatment of hepatic precancerous lesions. The former research showed this decoction had the effects of delaying the development of hepatic precancerous lesions. However, the exact mechanism of KXYA decoction is still ambiguous. Recent studies showed α5β1 integrin signal pathway had important effects on the stages of HCC while there is little report on hepatic precancerous lesions. Our preliminary study found that α5β1 integrin had abnormal expression in hepatic precancerous lesions, which can be regulated by KXYA decoction. Therefore, we hypothesize that the α5β1 integrin and its downstream PI3K/Akt signal pathway has an important role in hepatic precancerous lesions. In this study, we will use RT-PCR, WB and other techniques to observe the changes of α5β1 integrin/PI3K/AKT signaling pathway in liver precancerous lesions and the effects of intervention of KXYA decoction. This study will provides scientific basis for prevention and treatment of hepatic precancerous lesions.

肝癌前病变是肝癌发生必经阶段，如能有效逆转其病理进程，则可有效预防肝癌发生。抗纤抑癌方是我院专家用于治疗肝癌前病变的经验方，前期研究表明其具有延缓肝癌前病变进展作用，但具体机制未明。近年研究发现整合素α5β1及其信号通路在肝癌复发转移方面有着重要作用，但其在肝癌前病变中作用鲜见报道。我们初步研究发现整合素α5β1在肝癌前病变中有异常表达，抗纤抑癌方对其有调控作用，因而我们推测整合素α5β1下游PI3K/AKT信号通路在肝癌前病变中有着重要作用。本研究拟针对此假说，采用RT-PCR、WB等技术，从体内外实验来观察整合素α5β1/PI3K/AKT信号通路在肝癌前病变中变化情况及抗纤抑癌方对其干预作用。通过本研究为肝癌前病变防治提供科学依据。

肝癌前病变是肝癌发生必经阶段，如能有效逆转其病理进程，则可有效预防肝癌发生。抗纤抑癌方是我院专家用于治疗肝癌前病变的经验方，前期研究表明其具有延缓肝癌前病变进展作用，但具体机制未明。近年研究发现整合素α5β1及其信号通路在肝癌复发转移方面有着重要作用，但其在肝癌前病变中作用鲜见报道。我们初步研究发现整合素α5β1在肝癌前病变中有异常表达，抗纤抑癌方对其有调控作用，因而我们推测整合素α5β1下游PI3K/AKT信号通路在肝癌前病变中有着重要作用。本研究针对此假说，采用qPCR、WB等技术，从体内外实验来观察整合素α5β1/PI3K/AKT信号通路在肝癌前病变中变化情况及抗纤抑癌方对其干预作用。实验结果显示：1.在抗纤抑癌方干预肝癌前病变的作用疗效方面，通过体内实验，我们发现抗纤抑癌方可显著改善肝癌前病变大鼠的整体状态及肝脏组织病理表现，降低癌前特异性指标GST-Pi的表达；体外实验证实，抗纤抑癌方可抑制肝癌前病变细胞增殖。2.在抗纤抑癌方干预肝癌前病变的机制方面，本研究提示整合素α5β1/PI3K/Akt信号通路参与了肝癌前病变的形成过程，抗纤抑癌方可下调整合素α5β1/PI3K/Akt信号通路中相关基因与蛋白的表达，从而抑制细胞的异常增殖、延缓肝癌前病变的进展，其具体作用靶点与ITG-β1、FAK、PI3K高度相关。通过本研究为肝癌前病变防治提供科学依据。