大肠癌细胞膜磷脂变化与蛋白激酶C同工酶表达对肝转移影响的研究

目的　探讨结直肠癌细胞膜磷脂变化与蛋白激酶C(PKC)同工酶表达的关系及对肝转移的影响。　方法　采用高效液相色谱法 ,检测 5 8例大肠癌标本 (大肠癌原发灶、癌旁肠黏膜、肝转移灶 )的细胞膜磷脂酰肌醇 (PI)、磷脂酰丝氨酸 (PS)、磷脂酰乙醇胺 (PE)和磷脂酰胆碱 (PC)。用QRT PCR方法检测PKC α、 βⅡ、 δ、 ε、 λ、 ζ同工酶mRNA表达。　 结果　检测在癌原发灶、肝转移灶中 ,PI、PE、PC含量高于癌旁肠黏膜组织。肝转移灶与原发灶中PI、PC含量无显著性差异 (t =1 73,t=1 36 ,P >0 0 5 ) ,PE含量显著高于癌原发灶 (t=98 88,P <0 0 1)。癌原发灶和肝转移灶中PKC α表达水平降低。PKC βⅡ、 δ、 ε、 λ、 ζ表达高于癌旁肠黏膜组织 ,肝转移灶中PKC δ、 ε、 λ、 ζ表达高于癌原发灶 (t=4 31,P <0 0 5 )。PI、PC与PKC βⅡ呈正相关。PE与PKC δ、 ε、 λ、 ζ呈正相关 ,与PKC α呈负相关。　结论　细胞膜磷脂PI、PC增高 ,PKC α/PKC βⅡ比例改变与大肠癌发生有关。PE升高 ,PKC δ、 ε、 λ、 ζ增强表达促进结直肠癌肝转移。

Cell membrane phospholipid variation and protein kinase C expression effects on hepatic metastasis of large intestinal carcinoma

OBJECTIVE: To study cell membrane phospholipid variation and protein kinase C (PKC) isoenzyme expression and their effects on hepatic metastasis of large intestinal carcinoma. METHODS: High function liquid chromatography was used to separate and detect cell membrane phospholipids of phosphatidylinosital (PI), phosphatidylserine (PS), phosphatidylethanolamine (PE) and phosphatidylcholine (PC) in primary foci, paratumor intestine mucosa and hepatic metastasis of large intestinal carcinomas. And mRNA expression levels of PKC-alpha, -beta II, -delta, -epsilon, -lambda, -zeta isoenzymes were detected using QRT-PCR technique. RESULTS: Fifty-eight cases of colorectal cancer were examined. CONTENTS: of PI, PC and PE in primary foci and hepatic metastasis were higher than those in paratumor mucosa. PE content in hepatic metastasis was much higher than that in primary foci (t = 98.88, P < 0.01). But PI and PC contents had no significant differences between primary and hepatic metastasis (t = 1.73, 1.36, P > 0.05). PKC-beta II, -delta, -epsilon, -lambda, -zeta expression were enhanced in primary foci and hepatic metastasis, but PKC-alpha level decreased in comparison with paratumor mucosa. And PKC-delta, -epsilon, -lambda, -zeta levels in hepatic metastasis were higher than those in primary foci (t = 4.31, P < 0.05). PI and PC had positive correlations with PKC-beta II expression. PE had positive correlations with PKC-delta, -epsilon, -lambda, -zeta, but a negative correlation with PKC-alpha. CONCLUSIONS: The increases of PI and PC and PKC-alpha/PKC-beta II ratio change are related with colorectal cancer genesis. High content of PE and enhanced expression of PKC-delta, -epsilon, -lambda, -zeta isoenzymes and decreased PKC-alpha level improved hepatic metastasis of large intestinal carcinoma.