摘要
Background All-trans retinoic acid （ATRA） can influence the tumor cell proliferation cycle, and some chemotherapeutic drugs are cycle specific. In this study, we hypothesize that ATRA can enhance chemotherapeutic drug sensitivity by affecting the cell cycle of tumor cells.Methods The cell cycle of LoVo cells was evaluated using flow cytometry （FCM）. Cell viability was analyzed using the MTT assay. The morphologic changes in the treated LoVo cells were measured with acridine orange （AO）/ethidium bromide （EB） staining. Expression of survivin in LoVo cells was analyzed by immunofluorescence assay.Results After LoVo cells were treated with ATRA, the G0/G1 ratio of the tumor cells increased and the cell ratio of S-and G2/M-phase decreased. Viability of the cells decreased significantly after combined treatment with ATRA and 5-fluorouracil （5-FU） or mitomycin c （MMC） and was evaluated by fluorescence microscopy. Expression level of survivin in the tumor cells decreased after ATRA combination treatment.Conclusions ATRA enhances drug sensitivity of the LoVo cell line to cell cycle-specific agents and inhibits the expression of survivin in LoVo cells. The combination of ATRA and 5-FU or MMC promoted cell apoptosis, and the mechanism involved in apoptosis may be related to inhibition of survivin gene expression.
Background All-trans retinoic acid （ATRA） can influence the tumor cell proliferation cycle, and some chemotherapeutic drugs are cycle specific. In this study, we hypothesize that ATRA can enhance chemotherapeutic drug sensitivity by affecting the cell cycle of tumor cells.Methods The cell cycle of LoVo cells was evaluated using flow cytometry （FCM）. Cell viability was analyzed using the MTT assay. The morphologic changes in the treated LoVo cells were measured with acridine orange （AO）/ethidium bromide （EB） staining. Expression of survivin in LoVo cells was analyzed by immunofluorescence assay.Results After LoVo cells were treated with ATRA, the G0/G1 ratio of the tumor cells increased and the cell ratio of S-and G2/M-phase decreased. Viability of the cells decreased significantly after combined treatment with ATRA and 5-fluorouracil （5-FU） or mitomycin c （MMC） and was evaluated by fluorescence microscopy. Expression level of survivin in the tumor cells decreased after ATRA combination treatment.Conclusions ATRA enhances drug sensitivity of the LoVo cell line to cell cycle-specific agents and inhibits the expression of survivin in LoVo cells. The combination of ATRA and 5-FU or MMC promoted cell apoptosis, and the mechanism involved in apoptosis may be related to inhibition of survivin gene expression.
基金
The work was supported by Natural Science Foundation of Guangdong （No. 06021350）. Acknowledgements： We thank LIU Yang of the Duke University Medical Center in the United States for proofreading.
