Li Shi-Yong, Yu Bo, An Ping, Liang Zhen-Jia, Yuan Shu-Jun, Cai Hui-Yun
Department of General Surgery, Beijing Military General Hospital, Beijing 100700, China.
Hepatobiliary Pancreat Dis Int. 2004 Aug;3(3):411-6.
The molecular mechanism of hepatic metastasis of colorectal cancer is not well understood. The aim of this study was to assess the relations between phospholipid contents of cellular membrane and isoenzyme expression of protein kinase C (PKC) and their effects on hepatic metastasis of colorectal cancer.
High performance liquid chromatography was used to detect contents of cell membrane phospholipids: phosphatidylinosital (PI), phosphatidylserine (PS), phosphatidylethanolamine (PE) and phosphatidylcholine (PC) in primary foci, paratumor mucosa and hepatic metastatic foci in patients with colorectal carcinoma. The mRNA expression levels of PKC-alpha, -betaII, -delta, -epsilon, -lambda, -zeta isoenzymes were detected with the QRT-PCR technique.
The levels of PI, PC and PE in primary foci and hepatic metastatic foci were higher than those in paratumor mucosa. The level of PE in hepatic metastatic foci was much higher than that in primary foci (t=98.88, P<0.01); but the levels of PI and PC were not significantly different between primary foci and hepatic metastatic foci (t=1.73, 1.36, P>0.05). The expression levels of PKC-betaII, -delta, -epsilon, -lambda, -zeta were enhanced in primary foci and hepatic metastatic foci, but the level of PKC-alpha in primary foci was decreased as compared with that in paratumor mucosa. The levels of PKC-delta, -epsilon, -lambda, -zeta in hepatic metastatic foci were higher than those in primary foci. A positive correlation was observed between the expression levels of PI, PC and PKC-betaII and also between those of PE and PKC-delta, -epsilon, -lambda, -zeta. However, there was a close negative correlation between PE and PKC-alpha.
Increased levels of PI and PC and decreased ratio of PKC-alpha to PKC-betaII are related to colorectal cancer genesis. Increased levels of PE, increased expression of PKC-delta, -epsilon, -lambda, -zeta isoenzymes and decreased level of PKC-alpha are related to hepatic metastasis in colorectal carcinoma.
结直肠癌肝转移的分子机制尚未完全明确。本研究旨在评估细胞膜磷脂含量与蛋白激酶C(PKC)同工酶表达之间的关系及其对结直肠癌肝转移的影响。
采用高效液相色谱法检测结直肠癌患者原发灶、癌旁黏膜及肝转移灶中细胞膜磷脂: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)的含量。运用实时荧光定量聚合酶链反应(QRT-PCR)技术检测PKC-α、-βII、-δ、-ε、-λ、-ζ同工酶的mRNA表达水平。
原发灶和肝转移灶中PI、PC和PE的水平高于癌旁黏膜。肝转移灶中PE的水平显著高于原发灶(t = 98.88,P < 0.01);但原发灶与肝转移灶中PI和PC的水平差异无统计学意义(t = 1.73,1.36,P > 0.05)。PKC-βII、-δ、-ε、-λ、-ζ在原发灶和肝转移灶中的表达水平升高,但原发灶中PKC-α的水平低于癌旁黏膜。肝转移灶中PKC-δ、-ε、-λ、-ζ的水平高于原发灶。PI、PC与PKC-βII的表达水平之间以及PE与PKC-δ、-ε、-λ、-ζ的表达水平之间呈正相关。然而,PE与PKC-α之间呈密切负相关。
PI和PC水平升高以及PKC-α与PKC-βII的比值降低与结直肠癌的发生有关。PE水平升高、PKC-δ、-ε、-λ、-ζ同工酶表达增加以及PKC-α水平降低与结直肠癌肝转移有关。