Caspase-3 functions in the last step of caspase activation and plays an important role in apoptosis . PA has been shown to induce apoptosis through the caspase pathway . However, heat-inactivated PA does not have the capacity to induce apoptosis [26–27]. Consistent with previous reports, we found that inactivated PA did not induce apoptosis in pancreatic cancer cells. However, inactivated PA-MSHA was capable of inducing apoptosis in vitro. Therefore, we hypothesized that PA-MSHA could induce caspase-dependent apoptosis in tumor cells in vivo. Our data indicated that caspase-3 expression was reduced in pancreatic tumor tissue compared to normal pancreatic tissue, and that the level of cleaved caspase-3 increased in response to PA-MSHA treatment. The combination of PA-MSHA and NPT had a synergistic inhibitory effect on tumor growth. Overall, our data provide insight into the molecular mechanisms underlying PA-MSHA-induced apoptosis in pancreatic cancer cells. Because PA-MSHA inhibits pancreatic cancer cell proliferation and induces apoptosis, it may be a novel treatment for pancreatic cancer that can improve patient prognosis.