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.