中药白龙与HMBA对人癌周期细胞CKI-P16的调控

作者	单位
王代树	北京大学临床肿瘤学院北京肿瘤防治研究所
施学东	北京大学第一临床医学院骨科
梁云燕	北京大学临床肿瘤学院北京肿瘤防治研究所
刘军	北京大学临床肿瘤学院北京肿瘤防治研究所

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中文摘要:

目的 :研究中药白龙与西药环六亚甲基二乙酰胺 (HMBA)对人癌细胞中周期蛋白抑制因子P16的表达与调节。方法 :采用Northernblot、Westernblot等方法检测人癌细胞在白龙或HMBA作用下P16的表达调节。结果 :在白龙或HMBA作用下癌细胞G1期P16的表达增加 ,这一作用与cAMP PKA和DAC PKC两套信号通路共调节作用密切相关。当以PKA抑制剂阻断PKA通路时 ,P16表达下降 ,相反当PKC通路被阻断时P16表达水平升高。结论 :(1)癌细胞G1期P16的低表达 (与其他时相比较 )可能是P16不能有效抑制癌细胞恶性变化的重要原因。 (2 )白龙和HMBA对肿瘤细胞的增殖抑制机理与G1期细胞P16表达升高相关。 (3)白龙和HMBA对人癌细胞内P16的表达调节表现了中西药对肿瘤细胞调节机理的共性。 (4 )首次阐明了P16上游调控与cAMP/PKC信号通路密切相关。

英文摘要:

To study the regulation of bailong, a Chinese herbal anticancer preparation and hexamethylene bisacetamide (HMBA) on cyclin dependent kinase inhibitor P16 (CKI P16) genes in human cancer cells. Methods: The expression of CKI P16 in different human cancer cells treated by Bailong or HMBA under different condition, was examined using Northern hybridization, Western blotting assay, etc. Results: After being treated by Bailong or HMBA, the P16 expression increased. This effect was closely related to co regulation of cAMP PKA and DAC-PKC signal pathway. When PKA pathway was blocked with PKA inhibitor, the P16 expression decreased, while PKC pathway was blocked, it enhanced. Conclusion: (1)The low P16 expression in G 1 phase of cancer cell, as compared with that in S, G 2 and M phases, might be an important factor responsible to the incompetence of P16 in inhibiting effectively the malignant change of cancer cell. (2) Mechanism of Bailong and HMBA on cancer cell proliferation inhibition might be correlated with the enhancement of P16 expression in G 1 phase of cancer cells. (3) Regulation and expression of Bailong and HMBA on P16 showed the common character of Chinese and western medicine in regulating cancer cells. (4)This study elucidated that upstream of P16 was related to cAMP/PKC signal pathway closely.

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