Effect of protocadherins 10 re-expression induced by 5-aza-2&rsquo;-deoxycytidine on invasion and migration capacity of breast cancer cell line MDA-MB-231 and its mechanism

ZHANG Wei ZHU Wen-bin YUE Li-ling LIU Li-kun*

doi:10.16098/j.issn.0529-1356.2019.04.010

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Acta Anatomica Sinica ›› 2019, Vol. 50 ›› Issue (4) : 465-470. DOI: 10.16098/j.issn.0529-1356.2019.04.010

Effect of protocadherins 10 re-expression induced by 5-aza-2’-deoxycytidine on invasion and migration capacity of breast cancer cell line MDA-MB-231 and its mechanism

ZHANG Wei ^1,2 ZHU Wen-bin¹ YUE Li-ling¹ LIU Li-kun^1*

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Abstract

Objective To investigate whether re-expression of protocadherin 10(PCDH10) induced by 5-aza-2’-deoxycytidine (5-Aza-CdR) could affect the invasion and migration of MDA-MB-231 cells, and to explore the possible mechanism. Methods Human breast cancer cell line MDA-MB-231 was cultured in vitro. Control group and 5-Aza-CdR treatment group were set up. PCDH10 mRNA expression in MDA-MB-231 cell line was determined by reverse transcription-polymerase chain reaction (RT-PCR); Transwell chamber and wound healing assay were performed to measure the invasion and migration capacity of the cells, and protein expression of PCDH10, DNA methyltransferase(DNMT)3A, DNMT3B, nuclear factor(NF)-κB p65, matrix metalloproteinases(MMP)-2 and MMP-9 were detec Western blotting. Results 5-Aza-CdR could reverse the methylation status of PCDH10 gene in MDA-MB-231 cells in a dose-dependent manner. Re-expression of PCDH10 significantly inhibited cell invasion and migration capacity in vitro. Western blottoing analysis revealed that the expression of DNMT3A, DNMT3B, NF-κB p65, MMP-2 and MMP-9 in MDA-MB-231 cells were down-regulated after exposure to 5-Aza-CdR. Conclusion Re-expression of PCDH10 significantly inhibits MDA-MB-231 invasion and migration capacity. The inhibitory effect is characterized that 5-Aza-CdR treatment down-regulates DNMT3A and DNMT3B levels, recovers the expression of anti-oncogene PCDH10, further blocks the activation of NF-κB p65, resultsing in a decrease in the secretion of MMP-2 and MMP-9.

Key words

Breast cancer / Protocadherin 10 / Methylation / Invasion / Migration / RT-PCR / Western blotting / Human

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ZHANG Wei ZHU Wen-bin YUE Li-ling LIU Li-kun. Effect of protocadherins 10 re-expression induced by 5-aza-2’-deoxycytidine on invasion and migration capacity of breast cancer cell line MDA-MB-231 and its mechanism[J]. Acta Anatomica Sinica. 2019, 50(4): 465-470 https://doi.org/10.16098/j.issn.0529-1356.2019.04.010

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