局部治疗对残留肝细胞癌恶性生物学特性的影响及KLF6-KLF6-sv (TNF-a)-HSPs通路在其中的触发机制

肝细胞癌 (HCC)治疗复发后再次治疗难度增加，诱发机制不详。新近研究发现肿瘤恶性生物学特性与抑癌基因KLF6表达失活为其剪接异构体KLF6-sv关系密切。我们前期发现：栓塞化疗、热疗等局部治疗可促进残癌细胞内KLF6表达失活为KLF6-sv； KLF6-sv与HSPs（热休克蛋白）部分成员表达高度相关且来源同一细胞；肿瘤坏死因子a （TNF-a）可抑制残癌的部分恶性生物学特性。基于此，本研究拟对体内外HCC模型行热疗等局部治疗，观察残癌细胞转移、多药耐药等多种恶性生物学特性的变化；通过干预、刺激、定量、定位胞内KLF6、KLF6-sv、HSPs主要成员表达及TNF-a对相关通路的影响，正反两方面明确其相互关系。最终论证局部治疗通过对残留HCC恶性生物学特性的影响增加再次治疗的难度及KLF6-KLF6-sv (TNF-a)-HSPs通路在其中的触发作用，为彻底治疗HCC寻找高效靶点。

The triggering mechanism of enhanced difficulty for therapy on the recurrent hepatocellular carcinoma (HCC) is currently not clear. Recent researches show that the malignant biological character (MBC) of tumor tissue is closely linked to the inactivation of antitumor gene KLF6 in the form of its alternatively spliced isoform KLF6-SV. Our former research found that: For HCC, KLF6 can be further inactivatedly expressed into KLF6-SV by local therapy such as local embolization, heat therapy; The expression of some members of heat shock protein (HSPs) and KLF6-SV is closely correlated and co-localized in the same cell; The MBC of HCC can partly be inhibited by tumor necrosis factor (TNF-a). Basing what mentioned above, this study suppose to observe the MBC of post local therapy residual HCC, two-aspectly manifest the role of KLF6-sv, HSPs related pathway and the influence of TNF-a on them through inference, stimulate, quantity, localize their expression. The ultimate purpose is to demonstrate the supposition that the enhanced MBC of residual HCC can be induced by local therapy and its molecular mechanism of KLF6-KLF6-sv (TNF-a)-HSPs pathway. This study is supposed to find a new effective target pathway for thorough HCC therapy.