Shikonin induces apoptosis and necroptosis in pancreatic cancer via regulating the expression of RIP1/RIP3 and synergizes the activity of gemcitabine.

Pancreatic cancer is a lethal solid malignancy with poor prognosis. The optimal therapy for patients with advanced pancreatic cancer remains challenged. Thus, development of novel chemotherapy regimens is extremely urgent. Shikonin (SK) is a naphthoquinone derived from the roots of the Chinese medicinal herb Lithospermum erythrorhizon. It has been considered as effective anti-inflammatory, anti-oxidant, and anti-cancer activity agents in various diseases. In the present study, we found that SK inhibited the growth of human pancreatic cancer and enhanced the anti-tumor effect of gemcitabine in vitro and in vivo. Moreover, SK induced apoptosis and necroptosis in different pancreatic cancer cells by regulating RIP1 and RIP3 expression. The expression of RIP3 correlated with their necrotic response. These results suggest that the combination of SK and gemcitabine may be a promising chemotherapy regimen for pancreatic cancer.