EVALUATION OF CHEMOPREVENTIVE RESPONSE OF PENTOXIPHYLLINE AND SILDENAFIL IN COLORECTAL CARCINOMA EXPERIMENTALLY INDUCEDIN RATS: COMPARATIVE STUDY WITH 5-FLUOROURACIL
Keywords:1, 2 Dimethylhydrazines, 5-Flurouracil, Pentoxifylline, Sildenafil, Colorectal carcinoma, Carcinoembryonic antigen, carbohydrate antigen, Caspase-3
Objective: This study was designed to investigate some possible therapeutic mechanisms of pentoxifylline and sildenafil in the treatment of colorectal carcinoma induced by 1, 2 dimethylhydrazines in rats.
Methods: Rats were allocated into seven groups, negative control, colon cancer induced by 1,2,dimethylhydrazine, 5-fluorouracil (5-FU) (50 mg/kg)-treated, pentoxifylline (PTX) (50 mg/kg)-treated, sildenafil (0.7 mg/kg)-treated groups; the two other groups set as colon cancer induced group treated with PTX (50 mg/kg) plus 5-FU(50 mg/kg) and sildenafil (0.7 mg/kg) plus 5-FU (50 mg/kg), respectively.
Results: Biochemical results revealed significant elevation of serum carcinoembryonic antigen (CEA) levels, carbohydrate19-9 antigen (CA19-9) as colon cancer specific antigen markers; and a significant decrease in scaspase-3 (CASP3) as a marker for apoptosis, in the cancer-induced group compared to negative control group. Cancer-induced rats treated with 5-FU, with PTX or sildenafil showed a significant decrease in serum CEA and CA19-9 levels and a significant increase in CASP3 levels compared to cancer induced group. Furthermore, plasma levels of CEA and CA19-9 in 5-FU plus pentoxifylline and in 5-FUplus sildenafil groups were significantly decreased and plasma levels of CASP3 in 5-FU plus PTX, 5-FU plus sildenafil groups were significantly increased with respect to 5-FU treated group.
Conclusion: Results of the present study suggest a good therapeutic approach of the PDE inhibitors, PTX and sildenafil for intervention against progressive colon cancer with special reference to the induction of apoptosis in colon cancer cells.
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