ABSTRACT
Cytotoxic anti-neoplastic drugs are a kind of chemotherapeutic drugs that directly kill or inhibit the growth and proliferation of tumor cells, and it is one of the main drugs for the treatment of malignant tumors. These drugs may have toxic side effects on normal cells of human body (especially those with strong division and proliferation) when they are used to kill tumor cells. And patients may usually have adverse reactions even at a normal dose when using this kind of drugs. Due to the strong toxic side effects of cytotoxic chemotherapeutic drugs, their clinical application is limited. In recent years it has been found that aminopeptidase N inhibitor Ubenimex has a significant synergistic effect with anti-neoplastic chemotherapeutic drugs, which has the advantages of enhancing the therapeutic effect of drugs and reducing the toxic side effects of chemotherapeutic drugs. This review enumerates that the combination of Ubenimex and a variety of cytotoxic drugs can enhance the anti-tumor effect of cytotoxic drugs and reduce the occurrence of adverse reactions. In addition, the mechanism of combined use of Ubenimex in reversing drug resistance is also introduced. At the same time, is is further confirmed the clinical value of Ubenimex as an effective adjuvant in the treatment of malignant tumors, so as to provide a basis for clinical application.
ABSTRACT
<p><b>OBJECTIVE</b>To explore the effect of PI3K p85alpha gene silencing on the 5-fluorouracil (5-FU)-induced apoptosis of colorectal cancer cells.</p><p><b>METHODS</b>The PI3K p85alpha/RNAi transfected cells (PI3K p85alpha/RNAi-LoVo) were cultured in RPMI 1640 supplemented with 10% fetal calf serum and 500 microg/ml G418. The 50% inhibitory concentration (IC50) values of 5-FU (0.000625, 0.00125, 0.005, 0.01, 0.02, 0.04, 0.08, 0.16, 0.32 micromol/ml) were evaluated by MTT assay. Mitochondrial membrane potential was detected by JC-1 fluorescence, and Western blotting was used to analyze the expression of apoptotic proteins Bcl-6 and Bim.</p><p><b>RESULTS</b>Compared with the untransfected LoVo cells, PI3K p85alpha/RNAi-LoVo showed obviously decreased IC(50) of 5-FU (P=0.000). The mitochondrial membrane potential of PI3K p85alpha/RNAi-LoVo cells was significantly lower than that of LoVo cells, suggesting that silencing PI3K p85alpha expression increased the sensitivity of LoVo cells to 5-FU. The expression of apoptotic protein Bcl-6 and Bim were significantly higher in PI3K p85alpha/RNAi-LoVo cells treated with 5-FU than LoVo cells (P=0.000).</p><p><b>CONCLUSION</b>PI3Kp85alpha gene silencing can significantly promote 5-FU-induced apoptosis of colorectal LoVo cells.</p>