Norcantharidin combined with ABT-737 for hepatocellular carcinoma: Therapeutic effects and molecular mechanisms.
OBJECTIVE
To study the therapeutic effect of norcantharidin (NCTD) combined with ABT-737 on hepatocellular carcinoma cells and the molecular mechanism.


METHODS
Two hepatocellular carcinoma (HCC) cell lines, HepG2 and SMMC-7721, were selected. ABT-737 and NCTD were allocated into groups to be used alone or in combination. HepG2 and SMMC-7721 cells were cultured in vitro. Liver cancer cells in the logarithmic phase of growth were vaccinated and cultured to the cell wall stage; these cells were treated for 48 h with different concentrations of NCTD, or ABT-737, or NCTD combined with ABT-737. The cell proliferation inhibition rate was detected by methyl thiazolyl tetrazolium. The expression of Mcl in HCC cells was detected by Western Blotting, and the cells in each group after treatment had apoptosis detected by flow cytometry. The proliferation inhibition rate, the expression of Mcl-1 in cells and the apoptosis inducing effect of treatment were observed in each group, and the effect of NCTD on ABT-737 in the treatment of HCC and its mechanism of action were analyzed.


RESULTS
As the concentration of NCTD increased, the cell proliferation inhibition rate gradually decreased; and the treatment effect of ABT-737 1-3 μm combined with NCTD on cell proliferation inhibition was stronger than that of ABT-737 alone. The difference was statistically significant (P < 0.05). In observing the expression of Mcl-1 in cells after the treatment of different concentrations of NCTD, this was partially inhibited after treatment with NCTD 15 μm, and the expression of Mcl-1 was almost undetectable after treatment with NCTD 30 μm and 60 μm. The effect on inducing apoptosis with the treatment of ABT-737 or NCTD alone for 48 h was lower than that of the control group. The difference was not statistically significant (P > 0.05). The effect on inducing apoptosis in HepG2 and SMMC-7721 cells with the treatment of ABT-737 combined with NCTD for 48 h was greater than that of ABT-737 or NCTD alone. The difference was statistically significant (P < 0.05).


CONCLUSIONS
NCTD combined with ABT-737 has a positive role in the treatment of HCC, and it has great value in clinical research.
Jing Ren, Gang Li, Ling Lin, Tianjin Key Laboratory of Biomedical Detection and Instruments, Tianjin University, Tianjin 300072, China.
Jing
J
Ren
Jing Ren, Gang Li, Ling Lin, Tianjin Key Laboratory of Biomedical Detection and Instruments, Tianjin University, Tianjin 300072, China.
Gang
G
Li
Jing Ren, Gang Li, Ling Lin, Tianjin Key Laboratory of Biomedical Detection and Instruments, Tianjin University, Tianjin 300072, China.
Wen
W
Zhao
Jing Ren, Gang Li, Ling Lin, Tianjin Key Laboratory of Biomedical Detection and Instruments, Tianjin University, Tianjin 300072, China.
Ling
L
Lin
Jing Ren, Gang Li, Ling Lin, Tianjin Key Laboratory of Biomedical Detection and Instruments, Tianjin University, Tianjin 300072, China.
Tao
T
Ye
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001713:Biphenyl Compounds / Q000494:pharmacology*; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D045304:Cytochromes c / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D064549:Myeloid Cell Leukemia Sequence 1 Protein / Q000378:metabolism; D009596:Nitrophenols / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology*; D013997:Time Factors
C501332:ABT-737; D001713:Biphenyl Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; C579095:MCL1 protein, human; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009596:Nitrophenols; D010879:Piperazines; D013449:Sulfonamides; C069741:norcantharidin; D045304:Cytochromes c
Hepatocellular carcinoma cell; Mcl-1; Norcantharidin