Effects Of Doxorubicin On Tamoxifen And Expression Of Akt And Her-2 In MCF-7 Breast Cancer Cells

Objective:The incidence of breast cancer is increasing.It is the most common malignant tumor in women worldwide.Anthracyclines,such as Doxorubicin/Adriamycin(ADM),are among the most effective drugs for the treatment of breast cancer.ADM is a broad-spectrum anti-tumor drug with strong cytotoxicity that inhibits the growth of cancer cells by blocking the synthesis of DNA and RNA.Tamoxifen(TAM)is a commonly used drug for endocrine therapy of estrogen receptor-positive breast cancer[1].TAM is an anti-estrogen drug that competes with estrogen for binding to ER,blocks the action of estrogen,and prevents cancer cells from growing.Clinically,TAM is commonly used after patients undergo chemotherapy.This raises the question of whether chemotherapy affects the effects of endocrine therapy,and that metastatic recurrence of primary drug resistance in breast cancer endocrine therapy is clinically common and may be accompanied by changes in molecular markers.Akt,PI3K,ER,Her-2 and Ki67 play an important role in the molecular typing of breast cancer and the activation of related signaling pathways.In this in vitro experiment,ER-positive MCF-7 breast cancer cells were selected,and after doxorubicin treatment,the viability of cells and the changes of molecular markers such as Akt and Her-2 in cells were studied to study the effects of doxorubicin.Whether it affects the efficacy of tamoxifen and explore its related mechanisms.In addition,this experiment selects the expression of Akt in MCF-7 breast cancer cells after interference with doxorubicin,and examines the changes in the above indicators to explore the role of Akt.Methods:1.MCF-7 breast cancer cell line(ER,PR positive,Her-2 negative)was selected and cultured with doxorubicin to simulate clinical chemotherapy.2.Select MCF-7 breast cancer cell line and add endocrine drug tamoxifen to simulate clinical endocrine therapy.3.On the basis of doxorubicin culture,add the endocrine drug tamoxifen to simulate the endocrine therapy after the end of clinical chemotherapy.4.siRNA was used to interfere with the expression of Akt in normal MCF-7 breast cancer cells and long-term addition of doxorubicin.5.Using MTT to detect the inhibitory effect of long-term addition of doxorubicin on the proliferation of MCF-7 breast cancer cells and the ability of cells to interfere with Akt;MTT detection of tamoxifen after long-term addition of doxorubicin Inhibition of MCF-7 breast cancer cell proliferation.6.Western Blot was used to detect normal MCF-7 breast cancer cell lines,long-term addition of doxorubicin-treated cell lines,normal MCF-7 breast cancer cell lines(after interference),and long-term addition of doxorubicin,decreasing the expression of Akt,PI3K,ER,Her-2,and Ki67 in the cell line(after interference).Results:1.Tamoxifen inhibited MCF-7 breast cancer cells(P=0.003);while MCF-7 breast cancer cells lost doxorubicin,tamoxifen lost its inhibitory effect on cells(P=0.902).2.The proliferative capacity of MCF-7 cells cultured with long-term doxorubicin was significantly enhanced,while the proliferation of cells was decreased after siRNA interfered with Akt.3.The expression of Akt in MCF-7 breast cancer cell line was significantly increased after long-term addition of doxorubicin(P=0.031623),PI3K was slightly increased(P=0.18559),and ER expression increased significantly(P=0.008615),the expression of Her-2 was significantly increased(P=0.043352)and the expression of Ki67 was slightly increased(P=0.057361).4.After long-term addition of doxorubicin cultured MCF-7 breast cancer cell line interfered with by siRNA,the expression of Akt was significantly decreased(P=0.010137),the expression of PI3K was slightly decreased(P=0.341892),the expression of ER was significantly decreased(P=0.0192532),the expression of Her-2 was significantly decreased(P=0.014062),the expression of Ki67 was slightly decreased(P=0.071237).Conclusions:1.TAM can inhibit the growth of MCF-7 breast cancer cells.After doxorubicin treatment,the activation of signaling pathway,the expression of Her-2 and Akt is increased,which leads to the decrease of TAM,indicating that TAM inhibits cells after doxorubicin treatment.The effect is weakened.2.The proliferation of MCF-7 breast cancer cells was significantly enhanced after long-term addition of doxorubicin culture,and the expression of Akt was significantly increased.After the expression of Akt was interfered,the proliferation of MCF-7 cells decreased.3.After long-term addition of doxorubicin culture,the ER expression of MCF-7 breast cancer cells was significantly increased,and the expression of ER was significantly decreased after interfering with Akt expression.After long-term addition of doxorubicin culture,the expression of Her-2 in MCF-7 breast cancer cells was significantly increased,and the expression of Her-2 was significantly decreased after interfering with Akt expression.The target of Akt has a significant effect on the growth and survival of cancer cells.Breast cancer patients may benefit from the use of chemotherapy combined with Aktde targeted therapy.