Expressions of miRNA27a and miRNA451 in ovarian cancer and breast cancer cells and its correlation with drug resistance by targeting MDR1/P-glycoprotein
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Expressions of miRNA27a and miRNA451 in ovarian cancer and breast cancer cells and its correlation with drug resistance by targeting MDR1/P-glycoprotein
China OncologyVol. 25, Issue 3, Pages: 190-198(2015)
李智敏, 罗喜平, 曾俐琴. Expressions of miRNA27a and miRNA451 in ovarian cancer and breast cancer cells and its correlation with drug resistance by targeting MDR1/P-glycoprotein[J]. China Oncology, 2015, 25(3): 190-198.
李智敏, 罗喜平, 曾俐琴. Expressions of miRNA27a and miRNA451 in ovarian cancer and breast cancer cells and its correlation with drug resistance by targeting MDR1/P-glycoprotein[J]. China Oncology, 2015, 25(3): 190-198. DOI: 10.3969/j.issn.1007-3969.2015.03.006.
Expressions of miRNA27a and miRNA451 in ovarian cancer and breast cancer cells and its correlation with drug resistance by targeting MDR1/P-glycoprotein
Background and purpose: Resistance of cancer cells to chemotherapy is a major clinical obstacle to successful treatment and leads to poor prognosis for the patients. MicroRNA (miRNA) plays a vital role in tumor cells response to chemotherapeutic agents. This study plans to investigate the expressions of miRNA27a and miRNA451 in ovarian cancer and breast cancer cells and its correlation with drug resistance. Methods: A2780/Taxol cells were established using stepwise selection; Stem-loop quantitative real-time PCR (stem-loop RT-PCR) was used to detect expression of miRNA27a and miRNA451 in ovarian cancer and breast cancer cells. The A2780 and A2780/Taxol cells were transfected with the mimics or inhibitors of miRNA27a or negative control (NC) RNA and the mimics of miRNA451 or NC were transfected into MCF-7/ADM cells by Lipofectamine
TM
2000. The expression levels of MDR1 mRNA and P-glycoprotein (P-gp) were examined using RT-PCR and Western blot respectively. MTT method was used to analyze drug sensitivity. Results: The expression of miRNA27a was an average of (2.2±0.30) times higher in A2780/ Taxol cells than in A2780 cells
with a significant difference between the two groups (P0.05). The expression of miRNA451 was lower by 84% in MCF-7/ADM cells than in MCF-7 cells
with a significant difference between the two groups (P0.05). A2780/Taxol cells transfection with inhibitors of miRNA27a showed that the levels of MDR1 mRNA was decreased by (39±0.14)%
P-gp level [(26±5.3)%
]
decreased compared with the NC group [(43±6.7)%
]
the IC
50
(0.53 μmol/L) was less than the NC group (6.8 μmol/L)
and there was a significant difference between two groups (P0.05). Transfection of
A2780 cells with mimics of miRNA27a led to increase MDR1 mRNA expression by (121±0.11)% and decrease the sensitivity to paclitaxel (IC
50
: 0.2 μmol/L vs 0.06 μmol/L). There was a significant difference between two groups (P0.05). Transfection of MCF-7/ADM cells with mimics of miRNA451 showed that expression of MDR1 mRNA was decreased by (65±12)%
P-gp [(31±19)%
]
was less than the NC group [(83±12)%
]
the sensitivity of cells to adriamycin enhanced and the IC
50
of adriamycin (4.61 μmol/L) was less than the NC group (26 μmol/L)
and there was a significant difference between two groups (P0.05). Conclusion: The expressions of miRNA27a and miRNA451 are deregulated in A2780/Taxol and MCF-7/ADM cells respectively
which may play vital roles in drug resistance by regulating MDR1/P-gp expression directly or indirectly.
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Related Author
崔文贤
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Related Institution
常州市第七人民医院检验科
云南省肿瘤医院/ 昆明医科大学第三附属医院乳腺外一科
中山市人民医院乳腺外科
Department of Breast Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
Department of Breast Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital& Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College