Curcumin potentiates antitumor activity of gemcitabine in an orthotopic model of pancreatic cancer through suppression of proliferation, angiogenesis, and inhibition of nuclear factor-kappaB-regulated gene products

Cancer Res. 2007; 67(8):3853-61.

 

Pancreatic cancer is the 4th leading cause of mortality at present. Though it is highly reported type of cancer, the etiology is still a mystery. For any such reason due to overexposure, the cell lines may develop resistance which makes any therapy to work ineffectively.

Gemcitabine is one such therapeutic drug for pancreatic drug till date, but the cells show resistance to this drug which is making the treatment approach a little difficult. Gemcitabine treatment has also been resulted in objective tumor response rate of <10% and a marginal survival advantage in addition to multiple adverse events.

Hence, there is utmost attention required to find a better product which would both manage the growth of the tumor cells and sensitize pancreatic cancer cells to chemotherapy. Decades of research has shown that curcumin is a promising anti-inflammatory agent, which also enhances treatment response when given in combination.

 

Objective:

 To investigate whether curcumin can potentiate the antitumor effects of gemcitabine against pancreatic cancer cells growing in vitro and preclinical.

 

Study Design:

Pancreatic cell lines were pretreated with known dosage of curcumin. After 24 h of incubation, the cell lines were treated with gemcitabine. Then proliferation and apoptosis assay was conducted. To check the NF-κB activity, the experiment models were implanted with pancreatic cancer cells. After a week of infection the tumor cells were isolated and electrophoretic mobility shift assay was conducted.

 

Results:

Curcumin potentiated the apoptotic effects of gemcitabine in pancreatic cancer cells in vitro and significantly enhanced the antitumor effects of gemcitabine in orthotopic pancreatic tumors by downregulating NF-κB–regulated gene products and suppression of angiogenesis.

 

Conclusion:

Curcumin has the ability to potentiate the antitumor effects of gemcitabine by inhibiting NF-κB and its downstream targets, leading to the inhibition of proliferation, angiogenesis and invasion.

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