内分泌和化疗对乳腺肿瘤患者干细胞的影响

Effects of endocrine therapy and chemotherapy on stem cells in patients with breast cancer

BACKGROUND:Tumor stem cells are the root of cancer recurrence and metastasis, so clinical researches should focus on the effects of different treatments on tumor stem cells. OBJECTIVE:To explore the effects of endocrine therapy and chemotherapy on stem cells in patients with breast cancer. METHODS:After recovery and cultivation of estrogen receptor-positive human breast cancer cell lines MCF-7, passage 3 cells in logarithmic phase were selected and divided into three groups containing control, estradiol and estradiol with tamoxifen groups. The estradiol group was divided into three subgroups: 10^-7, 10^-8 and 10^-9 mol/L estradiol was added into the medium, respectively; the estradiol with tamoxifen group was divided into three subgroups: 10^-7, 10^-8 and 10^-9 mol/L estradiol with 10^-6 mol/L tamoxifen were added into the medium, respectively. The same amount of absolute ethyl ethanol was added into the medium of control group. Fifteen female patients with late recurrence and metastasis of breast cancer received chemotherapy as recurrence and metastasis group. Another 15 healthy volunteers were selected as healthy control group. RESULTS AND CONCLUSION:The proportion of CD44⁺CD24^-/low cell subsets in the estradiol and estradiol with tamoxifen groups was significantly higher than that of the control group (P < 0.05), and the proportion of CD44⁺CD24^-/low cell subsets in the estradiol group was significantly higher than that of the estradiol with tamoxifen group at the same concentration (P < 0.05). The proportion of CD44+CD24-/low cell subsets had no significant differences among groups at 10 and 20 days of culture (P < 0.05). The proportion of CD44⁺CD24^-/low cell subsets significantly increased in MCF-7 cells after 24-hour intervention with different chemotherapy drugs. But only the proportion of CD44⁺CD24^-/low cell subsets in the paclitaxel and doxorubicin groups was significantly higher than that of the control group after 20-day intervention (P < 0.05). Besides, the proportion of CD44⁺CD24^-/low cell subsets in the peripheral blood of healthy volunteers was significantly lower than that of the recurrence and metastasis group (P < 0.05). Among 15 patients with late recurrence and metastatic of breast cancer, 9 had stable disease, 5 had partial remission, 1 had failed chemotherapy and cancer progression. Moreover, the proportion of CD45^-CD44⁺CD24^-/low cell subsets in the peripheral blood of patients sensitive for chemotherapy was significantly lower than that before treatment (P < 0.05). In conclusion, both endocrine therapy and chemotherapy exert a certain effect on the CD44⁺CD24^-/low cell subsets of breast cancer positive for estrogen receptor. Given that CD44⁺CD24^-/low cell subsets in MCF-7 cells resist chemotherapy drugs, the proportion of CD45^-CD44⁺CD24^-/low cells in the peripheral blood of patients sensitive for chemotherapy is decreased.