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灵芝多糖对S180腹水瘤荷瘤小鼠肿瘤细胞核苷酸含量及细胞周期的影响

[Effect of Ganoderma lucidum polysaccharides on tumor cell nucleotide content and cell cycle in S180 ascitic tumor-bearing mice].

作者信息

Li Jian-jun, Lei Lin-sheng, Yu Chuan-lin, Zhu Zheng-guang, Zhang Qun, Wu Shu-guang

机构信息

Institute of Pharmaceutics, College of Pharmacy, Center of Instrument Analysis and Testing, Southern Medical University, Guangzhou 510515, China.

出版信息

Nan Fang Yi Ke Da Xue Xue Bao. 2007 Jul;27(7):1003-5.

Abstract

OBJECTIVE

To investigate the effect of Ganoderma lucidum polysaccharides (GLP) on the nucleotide contents and cell cycle distribution of the tumor cells in S180 ascitic tumor-bearing mice and explore the possible mechanism of the antitumor effect of GLP.

METHODS

Mice bearing S180 ascitic tumor were subjected to intragastric administration of GLP (100, 200, and 400 mg/kg), normal saline or subcutaneous injection of cyclophosphamide (CTX) at 25 mg/kg, respectively. The treatment was given once daily for 9 consecutive days, after which the ascitic tumor cells were harvested for determination of the RNA and DNA contents and their ratio as well as the cell cycle alterations. Laser scanning confocal microscopy and acridine orange staining was performed to evaluate the DNA and RNA fluorescence intensity, and flow cytometry with propidium iodide (PI) staining was utilized for cell cycle analysis of the tumor cells.

RESULTS

Compared with normal saline group, the tumor cells in the 3 GLP groups all showed reduced RNA and DNA contents, and this reduction was statistically significant in 200 mg/kg GLP group (P=0.000). Significantly reduced RNA/DNA ratio was noted in all the 3 GLP groups (P=0.003, 0.000, 0.008 corresponding to 400, 200, and 100 mg/kg groups), suggesting that ganoderma polysaccharides more effectively reduced RNA content than DNA content. CTX also resulted in reduced RNA and DNA contents but not the RNA/DNA ratio. At the doses of 400, 200, and 100 mg/kg, GLP increased the percentage of G2/G2 phase cells (P=0.003, 0.000, and 0.000) whereas CTX showed the contrary effect (P=0.000). GLP produced no obvious effect on S-phage cells but CTX significantly reduced their percentage (P=0.000). GLP at the 3 doses all decreased the percentage of G2/M phase tumor cells (P=0.014, 0.049, 0.016) and CTX again induced contrary effect (P=0.000).

CONCLUSION

With different effects from CTX on DNA and RNA contents and cell cycle, GLP inhibits DNA and RNA synthesis in the tumor cells by mobilizing the host immune function to interfere with the normal cell cycles, which might be one of the mechanisms for the antitumor effect of GLP.

摘要

目的

研究灵芝多糖(GLP)对S180腹水瘤小鼠肿瘤细胞核苷酸含量及细胞周期分布的影响,探讨GLP抗肿瘤作用的可能机制。

方法

将接种S180腹水瘤的小鼠分别给予GLP(100、200和400mg/kg)灌胃、生理盐水灌胃或皮下注射25mg/kg环磷酰胺(CTX)。连续9天每天给药1次,之后收集腹水瘤细胞,测定RNA和DNA含量及其比值以及细胞周期变化。采用激光扫描共聚焦显微镜和吖啶橙染色评估DNA和RNA荧光强度,并用碘化丙啶(PI)染色的流式细胞术对肿瘤细胞进行细胞周期分析。

结果

与生理盐水组相比,3个GLP组的肿瘤细胞RNA和DNA含量均降低,其中200mg/kg GLP组降低具有统计学意义(P = 0.000)。3个GLP组的RNA/DNA比值均显著降低(400、200和100mg/kg组分别为P = 0.003、0.000、0.008),表明灵芝多糖降低RNA含量比降低DNA含量更有效。CTX也导致RNA和DNA含量降低,但未影响RNA/DNA比值。在400、200和100mg/kg剂量下,GLP增加了G2/G2期细胞百分比(P = 0.003、0.000和0.000),而CTX则产生相反作用(P = 0.000)。GLP对S期细胞无明显影响,但CTX显著降低了其百分比(P = 0.000)。3个剂量的GLP均降低了G2/M期肿瘤细胞百分比(P = 0.014、0.049、0.016),CTX再次产生相反作用(P = 0.000)。

结论

GLP对DNA和RNA含量及细胞周期的影响与CTX不同,它通过调动宿主免疫功能干扰正常细胞周期来抑制肿瘤细胞的DNA和RNA合成,这可能是GLP抗肿瘤作用的机制之一。

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