Bibliographic Details
| Title: |
Hedyotis diffusa Willd overcomes 5-fluorouracil resistance in human colorectal cancer HCT-8/5-FU cells by downregulating the expression of P-glycoprotein and ATP-binding casette subfamily G member 2. |
| Authors: |
QIONGYU LI1, XIANGFENG WANG2, ALING SHEN1,3, YUCHEN ZHANG1, YOUQIN CHEN4, SFERRA, THOMAS J.4, JIUMAO LIN1,3 jiumaolin@hotmail.com, JUN PENG1,3 pjunlab@hotmal.com |
| Source: |
Experimental & Therapeutic Medicine. Nov2015, Vol. 10 Issue 5, p1845-1850. 6p. |
| Subject Terms: |
*FLUOROURACIL, *HEDYOTIS, *FLUOROPYRIMIDINES, *ANTINEOPLASTIC agents, *CARCINOGENS, *CYTOPROTECTION |
| Abstract: |
Previous studies have demonstrated that Hedyotis diffusa Willd (HDW), a traditional Chinese herbal medicine, exhibits potent anticancer activity in models of colorectal cancer (CRC). Aggressive forms of CRC exhibit resistance to widely used chemotherapeutic drugs, including the antimetabolite, 5-fluorouracil (5-FU); however, less is known with regard to the activity of HDW against 5-FU-resistant cancer. In the present study, the mechanism of action and the potency of ethanol extracts of HDW (EEHDW) were investigated on a multidrug-resistant CRC HCT-8/5-FU cell line. Using an MTT cell proliferation assay, EEHDW treatment was shown to significantly reduce the cell viability of HCT-8/5-FU cells in a dose- and time-dependent manner. Furthermore, EEHDW significantly increased the retention of the ATP-binding cassette (ABC) transporter substrate, rhodamine-123, as compared with the untreated controls. To further investigate the molecular mechanisms targeted by EEHDW in the resistant cells, the expression levels of the ABC drug transporter protein, P-glycoprotein (P-gp), and ABC subfamily G member 2 (ABCG2), were analyzed using reverse-transcription polymerase chain reaction and western blot analysis. The mRNA and protein expression levels of P-gp and ABCG2 were reduced in the HCT-8/5-FU cells following EEHDW treatment, indicating that EEHDW inhibits ABCG2-mediated drug resistance by downregulating the expression of ABCG2 and P-gp. Therefore, the potential application of EEHDW as a chemotherapeutic adjuvant represents a promising alternative approach to the treatment of drug-resistant CRC. [ABSTRACT FROM AUTHOR] |
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| Database: |
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