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n‐3 Polyunsaturated fatty acids enhance the antitumor effect of 5‐fluorouracil by inhibiting bcl‐2 and mutant‐p53
Author(s) -
Tan YaoZong,
Huang WenGe,
Chen FengYing,
Li Jie,
Zhou JingYa,
Wang LiJun,
Chen Li,
Zhu HuiLian
Publication year - 2013
Publication title -
european journal of lipid science and technology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.614
H-Index - 94
eISSN - 1438-9312
pISSN - 1438-7697
DOI - 10.1002/ejlt.201300017
Subject(s) - polyunsaturated fatty acid , apoptosis , tunel assay , fluorouracil , chemistry , immunohistochemistry , colorectal cancer , cancer , medicine , endocrinology , cancer research , biochemistry , biology , fatty acid
The study determined whether n‐3 polyunsaturated fatty acids (n‐3 PUFAs) enhance the chemotherapeutic ability of 5‐fluorouracil (5‐FU) to affect bcl‐2 and mutant‐p53 (mt‐p53). Thirty‐two BalbC/c mice bearing SW480 colorectal cancer (CRC) xenografts were randomly divided into four groups and fed with basic diet (5% of fat) and diets (20% of fat) with 0.69, 14.84, and 24.27% of n‐3 PUFAs, while all mice received 5‐FU injections (35 mg/kg) every 3 days. After 21 days' treatment, tumors were subjected to HE staining, TUNEL staining, and immunohistochemical analyses for bcl‐2 and mt‐p53, and serum n‐3 PUFAs composition were determined by GC‐FID. The proportion of serum n‐3 PUFAs increased in the high (17.1%) and low (12.3%) n‐3 groups (vs. 3.1% in control). The high n‐3 group showed slower tumor growth (Δvolume: 370.3 mm 3 vs. 556.9 mm 3 , p < 0.05), larger tumor necrosis areas with more loosely arranged cells, and greater tumor cell apoptosis (positive rate: 9.4% vs. 2.2%, p < 0.05) compared to the control. Both Bcl‐2 and mt‐p53 expressions were inversely and dose‐dependently correlated to dietary n‐3 PUFAs (all p < 0.05). n‐3 PUFAs enhance the antitumor effect of 5‐FU on SW480 xenografts probably through promoting tumor apoptosis via inhibiting bcl‐2 and mt‐p53. Practical applications: n‐3 PUFAs have distinct anti‐cancer capacity and combination of n‐3 PUFAs and 5‐FU was considered as a potential approach for cancer chemotherapy, but the exact mechanism of the co‐anticancer effect of n‐3 PUFAs is still not clarified. Our present study demonstrated that n‐3 PUFAs increase the apoptosis of CRC cells by inhibiting the expression of bcl‐2 and mt‐p53. These results highlight the pro‐apoptosis effect of n‐3 PUFAs and reveal the possible mechanism of this effect. The main strategy of chemotherapy regimens is to enhance the pro‐apoptosis capacity of drugs against malignancy and n‐3 PUFAs, as a kind of dietary nutrient, are easy to be obtained and cause no toxicity compared with other anti‐cancer drugs. In this context, n‐3 PUFAs may be developed as adjuvant anti‐cancer agent combining with 5‐FU or even other drugs.