達瑪烷苷元和癌基因以及抑癌基因
Dammarane Saponins, Oncogene and tumor inhibiting gene
邱國松
癌基因是一組編碼生長因數、蛋白激酶、或轉錄因數的基因。當前的研究表明,但癌基因的表達異常時,它和腫瘤的發生和發展密切相關。癌基因表達異常通常是由於基因突變、基因表達失調控、以及抑癌基因的功能抑制等引起,它的表達異常使得正常細胞向癌細胞轉化,並最終發展成腫瘤。
大量的研究表明:二醇組和三醇組來源的達瑪烷苷元能夠抑制生長因數類的癌基因表達。例如,在一系列的腫瘤細胞中(包括原隨細胞性白血病HL-60細胞),aPPD、aPPT以及人參總皂苷均能抑制癌基因c-fos和c-jun的表達1, 2。同樣,aPPD的前體化合物Rk1能夠通過抑制癌基因c-myc的表達,從而顯著地抑制肝癌HepG2細胞的生長3。再者,二醇組和三醇組達瑪烷苷元以及皂苷Rh2(一個aPPD的前體化合物)也能抑制癌細胞BALB/c3T3 A31-1-1、A31-1-13、和NIH3T3細胞內癌基因cdk2的表達,從而阻斷細胞週期的進展和細胞分裂,從而達到抑制腫瘤的目的4, 5。
達瑪烷苷元不僅通過抑制癌基因的表達來發揮抗腫瘤作用,還能通過啟動抑癌基因來加強這種作用。例如在雌激素敏感的乳腺癌MCF-7細胞和雌激素不敏感的乳腺癌MDA-MB-231細胞中,從西洋參中提取的達瑪烷苷元能顯著地提高抑癌基因p21的表達(p21蛋白是一種抑制細胞週期進展的調控蛋白),從而抑制細胞週期的進展和癌細胞增殖6。除此之外,在一系列的腫瘤細胞中(包括NIH3T3、U937人單核細胞白血病細胞、骨肉瘤MG-63細胞、和肝癌SMMC7721細胞),達瑪烷苷元(包括Rg1)能夠增加抑癌基因p53、p21和Rb的表達;這些關鍵抑癌基因表達水準的增加能夠使細胞分裂停頓,並且誘導腫瘤細胞凋亡,從而發揮抗腫瘤的作用4, 7, 8。
參考文獻:
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