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Vitamin D Enhances the Efficacy of Irinotecan through miR-627-Mediated Inhibition of Intratumoral Drug Metabolism
Cytochrome P450 enzyme CYP3A4 is an important drug-metabolizing enzyme, and high levels of tumoral expression of CYP3A4 are linked to drug resistance. We investigated the function of vitamin D–regulated miR-627 in intratumoral CYP3A4 suppression and its role in enhancing the efficacy of chemotherapy. We found that miR-627 targets CYP3A4 and suppresses CYP3A4 expression in colon cancer cell lines. Furthermore, calcitriol (the active form of vitamin D) suppressed CYP3A4 expression by activating miR-627. As a result, calcitriol inhibited CYP3A4-mediated metabolism of irinotecan (a topoisomerase I inhibitor) in cancer ce...
Source: Molecular Cancer Therapeutics - August 31, 2016 Category: Cancer & Oncology Authors: Sun, M., Zhang, Q., Yang, X., Qian, S. Y., Guo, B. Tags: Small Molecule Therapeutics Source Type: research

Vitamin D Inhibits Intratumoral Drug Metabolism
Cytochrome P450 enzyme CYP3A4 is an important drug-metabolizing enzyme, and high levels of tumoral expression of CYP3A4 are linked to drug resistance. We investigated the function of vitamin D–regulated miR-627 in intratumoral CYP3A4 suppression and its role in enhancing the efficacy of chemotherapy. We found that miR-627 targets CYP3A4 and suppresses CYP3A4 expression in colon cancer cell lines. Furthermore, calcitriol (the active form of vitamin D) suppressed CYP3A4 expression by activating miR-627. As a result, calcitriol inhibited CYP3A4-mediated metabolism of irinotecan (a topoisomerase I inhibitor) in cancer ce...
Source: Molecular Cancer Therapeutics - August 31, 2016 Category: Cancer & Oncology Authors: Sun, M., Zhang, Q., Yang, X., Qian, S. Y., Guo, B. Tags: Small Molecule Therapeutics Source Type: research