| Colon cancer is a serious malignant type of cancer in the world. Acquisition of multi-drug resistance (MDR) during
chemotherapy is still a controversial challenge during cancer treatment. Accordingly, detection of safe and
impressive MDR-reversing targets such as microRNAs (miRNAs/miRs) can play critical role in cancer treatment.
Here, the functional effects of miR-29a in chemo-resistant colon cancer cells is scrutinized. The effect of doxorubicin
(DOX) on cell proliferation after miR-29a transfection has been evaluated using MTT assay in HT29 and
HT29/DOX cells. Rhodamine123 (Rh123) assay is used to identify the activity of common drug efflux through
membrane transporters P-glycoprotein (P-gp). P-gp and PTEN mRNA/protein expression levels were measured
by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blot analyses. Flow cytometry
was employed to the investigation of apoptosis. ANOVA followed by Bonferroni's and Sidak's tests were
used to compare the data from different groups. Thus, it was shown that miRNA-29a overexpression considerably
inhibited the HT29/DOX viability. miR-29a significantly down-regulated P-gp expression and activity in HT29/
DOX cells and declined drug resistance through elevation of intracellular DOX. Furthermore, upon miRNA-29a
transfection, PTEN expression could be restored in resistant cells. These results have indicated that miR-29a target
PTEN ultimately P-gp, which is downstream of PTEN, inhibit drug resistance, proliferation, and apoptosis
through PI3K/Akt pathway. As a result, miR-29a overexpression is led to enhance the sensitivity of HT29/DOX
cells to DOX-treatment by targeting P-gp. MiR-29a might proffer a novel promising candidate for colon cancer
therapeutics during chemotherapy. |