Effects of Jianpi Jiedu Recipe on reversion of P-glycoprotein-mediated multidrug resistance through COX-2 pathway in colorectal cancer / 中国结合医学杂志
Chinese journal of integrative medicine
; (12): 610-617, 2014.
Article
в En
| WPRIM
| ID: wpr-293283
Ответственная библиотека:
WPRO
ABSTRACT
<p><b>OBJECTIVE</b>To evaluate the underlying mechanism of Jianpi Jiedu Recipe (, JJR) in the reversion of multidrug resistance concerning colorectal cancer in vitro and in vivo.</p><p><b>METHODS</b>Mice were treated orally with JJR at a daily 4.25 g/(kg·day) or injected with vinblastine (VCR) 2.5 mg/(kg·day) for 3 weeks after having been inoculated with HCT8/V cells; tumor tissues were assayed by hematoxylin and eosin staining. Firstly, the effects of JJR on the expression of cyclooxygenase-2 (COX-2) were tested by real-time polymerase chain reaction (PCR) technique and COX-2 gene silenced by siRNA. Secondly, the variation of intracellular concentration of oxaliplatin (L-OHP) was evaluated by the inductively coupled plasma mass spectroscopy (ICPMS) in HCT8/V and its COX-2 siRNA cells; the concentration of JJR combined with chemotherapeutic drugs and the reverse effect of multidrug resistance (MDR) in HCT8/V cells was evaluated by the MTT assay. Thirdly, real-time quantitative PCR and Western blot analysis were used to detect the multidrug resistance gene 1 (MDR1) mRNA and P-gp expression.</p><p><b>RESULTS</b>JJR had an inhibitory effect on the growth of tumors in vivo, and it, in combination with chemotherapeutic drugs, could reverse the drug-resistance of HCT8/V cells and increase the sensitivity of HCT8/V cells to VCR, DDP, 5-Fu, and THP. ICP-MS results showed that JJR could increase the concentration of drugs in HCT8/V cells (P<0.01). Furthermore, it was shown that JJR could reverse drug resistance of colorectal cancer cells by decreasing MDR1 expression and P-gp level via downregulation of COX-2, which has been represented as one of the major mechanisms that contributes to the MDR phenotype (P<0.01).</p><p><b>CONCLUSION</b>JJR reversed multidrug resistance and enhanced the sensitivity to chemotherapy, which could be attributed to the down-regulation of COX-2 in MDR1/P-gp-mediated MDR colorectal cancer after chemotherapy.</p>
Полный текст:
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База данных:
WPRIM
Основная тема:
Organoplatinum Compounds
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Pathology
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Pharmacology
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Vinblastine
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Drugs, Chinese Herbal
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Colorectal Neoplasms
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Signal Transduction
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ATP Binding Cassette Transporter, Subfamily B, Member 1
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Drug Resistance, Multiple
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Drug Resistance, Neoplasm
Пределы темы:
Animals
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Female
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Humans
Язык:
En
Журнал:
Chinese journal of integrative medicine
Год:
2014
Тип:
Article