Effects of STAT3 aberrant activation on malignant transformation of human umbilical cord mesenchymal stem cells when exposed to human breast cancer microenvironment / 基础医学与临床

ABSTRACT

Objective_To investigate whether hUCMSCs undergo malignant transformation when exposed to MCF-7B breast cancer microenvironment and whether the abnormal activation and over expression of STAT3 play an impor-tant role in this transformation.Methods_The experiment was divided into three groupsblank group ( hUCMSCs were separately cultured),experimental group(hUCMSCs were indirectly co-cultured with MCF-7B breast cancer cells),positive control group(MCF-7B breast cancer cells were separately cultured).Morphology of cells was detec-ted by invertedmicroscope.Cell cycle was detected by flow cytometry.The mRNA expression of STAT3, c-Myc and Bcl-xL was tested by real-time PCR.The protein expression and location of p-STAT3,c-Myc and Bcl-xL were detected by immunofluorescence.The protein expressions of p-STAT3,STAT3,c-Myc and Bcl-xL were also meas-ured by Western blot.Results_The experimental group cells showed typical morphology of the tumor cells.The cells proportion of experiment group in G1 phase was significantly lower than that of the blank group(P<0.05),but which in S and G2 phase were significantly higher than those of the blank group(P<0.05).The mRNA expression levels of STAT3 ,c-Myc and Bcl-xL in experimental group was significantly higher than those in blank group ( P<0.05).p-STAT3,STAT3,c-Myc and Bcl-xL protein were significantly higher than those of the blank group(P<0.05),and they were mainly located in the nuclei.The protein expression of STATS also showed significant changes in experimental group.Conclusions_hUCMSCs trends to malignant transformations when exposed to MCF-7B breast cancer microenvironment.The abnormal activation and over expression of STAT3 are of important factors leading to the malignant transformation of hUCMSCs.