The Study Of HER2 Expression In Breast Cancer Resistance

Objective:In recent years,the incidence of breast cancer has been increased gradually,and it has become the highest incidence of malignant tumors in women.In clinic,breast cancer recurrence and metastasis are very common,and are often accompanied by the molecular marker of breast cancer.These patients often develop rapidly,and systemic metastasis occurs soon.HER2,ER,K167,PI3K,Akt and MDR have an important role in molecular classification of breast cancer,activating the signal transduction pathway and drug resistance.This study gives the breast cancer cells long-term low-dose doxorubicin to simulate the effect of clinical long-term chemotherapy.Then,we detect and compare the HER2,ER,K167,PI3K,Akt and MDR change in breast cancer cells.In addition,in order to study the role and effect of HER2 on other indicators,we interfere with the expression of HER2 in long-term low-dose doxorubicin cells,and then detect the corresponding changes in other indicators,so as to explain their relationship.Methods:1.Select breast cancer cell line SKBR3(HER2 positive;ER,PR negative),give long-term chemotherapy drug:doxorubicin.,in order to simulate the clinical situation that need recept the long-term chemotherapy.2.The difference of cell proliferation between normal SKBR3 cell line and long time doxorubicin cell line was detected by MTT.3.The expression of HER2 of long time doxorubicin cell line was interfered by siRNA-HER2.4.Western blot was used to detect the changes in the expression of HER2 in SKBR3 cell lines,long time doxorubicin cell lines and interfering cell lines.5.The expression of ER,PI3K,Akt,MDR and KI67 of SKBR3 cell line,long time doxorubicin cell line and interfering cell strain were detected by Western blot.Results:1.Results showed that the expression of HER2 increased significantly after SKBR3 cells were added to doxorubicin for a long time(P= 0.001173),HER2 decreased significantly after siRNA interfere HER2 expression(P= 0.000838).2.PI3K increased significantly after long-term administration of doxorubicin(P=0.029905).After interfering with HER2 expression,PI3K expression decreased slightly(P=0.102762).3.Akt increased significantly after long-term administration of doxorubicin(P=0.000876).After interfering with HER2 expression,Akt significantly decreased(P=0.000378).4.The expression of ER in SKBR3 cells was significantly decreased after long term addition of doxorubicin(P=0.013492).After interfering with HER2 expression,ER increased(P=0.021968).5.The expression of MDR in SKBR3 cells was increased slightly after long term addition of doxorubicin(P= 0.119728).After interfering with HER2 expression,MDR continues to rise(P= 0.300654).6.The expression of KI67 in SKBR3 cells decreased slightly after long-term doxorubicin stimulation(P= 0.4540675).After interfering with HER2,KI67 expression increased slightly(P= 0.1391941).7.The MTT results showed that the growth rate of long time doxorubicin cell lines was significantly faster than that of normal SKBR3 cell lines,P = 0.000290508.Conclusions:1.After a long time of doxorubicin treatment,the cell growth rate of SKBR3 cells increased and HER2 expression increased.(when we use doxorubicin for a short time,we observed that the growth rate of SKBR3 cells slowed down significantly.)2.After long time doxorubicin treatment,the expression of PI3K in SKBR3 cellsincreased significantly,and the expression of Akt increased.3.After long time doxorubicin treatment,the expression of ER in SKBR3 cells decreased significantly.4.After long time doxorubicin treatment,the expression of MDR in SKBR3 cells increased slightly,but there was no statistical difference.5.After long time doxorubicin treatment,the expression of KI67 in SKBR3 cells decreased slightly,and KI67 increased slightly after interfering with HER2 expression.There is a trend that the expression of HER2 increased,the expression of KI67 decreased,while the expression of HER2 decreased,and the expression of KI67 increased.6.After interfering the HER2 expression of SKBR3 cells that with long time doxorubicin,the expression of HER2 decreased obviously,the expression of Akt decreased obviously,the expression of ER increased obviously,the expression of PI3K decreased slightly,the expression of MDR was higher slightly.