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Alexandria Journal of Medicine

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The effects of valproic acid on the mRNA expression of Natriuretic Peptide Receptor A and KQT-like subfamily Q-1 in human colon cancer cell lines

Mona Hajikazemi, Hoda Sohrabi, Ahad Yamchi, Mohsen Saeedi

Abstract


Aim and objectives: The histone deacetylase (HDAC) inhibitor, Valproic Acid (VPA), causes growth inhibition and apoptosis in colorectal cancer cells. HDAC inhibition is associated with the transcriptional regulation of Natriuretic Peptide Receptor-A (NPR-A). NPR-A regulates voltage-gated potassium channel, KQT-like subfamily Q, member 1 (KCNQ1). NPR-A and KCNQ1 are also involved in the initiation and propagation of cancer cells. In this study, we investigated the simultaneous expressional changes of NPR-A and KCNQ1 among VPA-treated colon cancer cells.

Materials and methods: Human colorectal cancer cells were cultured and treated with increasing concentrations of VPA at different time points. MTT viability test was conducted to evaluate the growth inhibition. Real Time RT-PCR was used to quantify differential mRNA expression of NPR-A and KCNQ1 genes. Two-way ANOVA and bonferroni post-tests were used to analyze data statistically.

Results: We showed that VPA treatment inhibits the growth of SW-480 cells more efficiently compared to HT-29. NPR-A and KCNQ1 genes were significantly upregulated upon VPA treatment in both cell lines (P < 0.0001).

Conclusion: The alteration of NPR-A and KCNQ1 genes were more ordered among SW-480 cancer cells. The expressional changes of KCNQ1 and NPR-A among VPA treated human colon cancer cells follow the same pattern in similar combinations. VPA could regulate the expression of KCNQ1 through altering the mRNA expression of NPR-A.

Keywords: Colorectal cancer, Human colorectal cancer cell lines, KCNQ1, Natriuretic Peptide Receptor A, Valproic acid




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