Abstract 1107: Co-treatment with a C1B5 domain peptide of protein kinase Cγ and a low dose of gemcitabine effectively inhibited pancreatic cancer growth in mouse peritoneal cavity

Although the gemcitabine is an effective chemotherapeutic agent for pancreatic cancer, unacceptable side effects often accompany. Since we have previously discovered that PKCγ C1B domain peptides effectively control tumor growth without any side effect (Kawabata et. al, Cancer Biol Ther, 2012), we sought to examine the efficacy of co-treatment with this peptide and a low dose of gemcitabine on the growth of pancreatic cancer. Although individual and co-treatment with C1B5 peptide (1µM) and gemcitabine (20 nM) weakly inhibited growth of PAN02 murine pancreatic acinar cell carcinoma in 2D culture, either treatment effectively attenuated spheroid growth on PAN02 cells in 3D culture with 48.2% and 35.8% inhibition, respectively. Combination treatment with the C1B5 peptide and gemcitabine further attenuated the growth of PAN02 cells (69.5% inhibition). In mice bearing peritoneal allograft tumors of PAN02 cells (2.5 x 105 cells/mouse), combination treatment with C1B5 peptide at 20 mg/kg (every other day) and gemcitabine 15 mg/kg (every three days) markedly inhibited tumor growth of PAN02 allografts (94% inhibition) more than individual treatment with gemcitabine (76% inhibition) or C1B5 peptide (39% inhibition). The tumor growth inhibition by the combination treatment was similar to the higher dose (50 mg/kg) of gemcitabine alone treatment. Peritoneal cavity infiltrated neutrophils and granzime B+ lymphocyte numbers were significantly higher in combination treatment group than in control group. In cell culture study, the treatment with C1B5 peptide alone (1µM) significantly increased INF-γ, IL-2, and TNF-α mRNA levels, suggesting that C1B5 peptide directly stimulated Jurkat cell activation. These studies suggest that stimulation of leucocyte migration toward cancer tissues and activation of cytotoxic T cells may play important roles in tumor growth attenuation by the combination treatment of C1B5 peptide and gemcitabine. Taken together, the current study suggests that C1B5 peptide offers an effective combination treatment strategy to reduce side effects associated with gemcitabine without losing tumoricidal effect of this agent. This work is supported in part by Kansas State University Johnson Cancer Research Center, NIH grants P20 GM103418, and Kansas State Bioscience Authority Collaborative Cancer Research grant. Citation Format: Alejandro Zulbaran, Kelsey Monson, Susumu Ishiguro, Atsushi Kawabata, Deepthi Uppalapati, Naomi Ohta, Masaaki Tamura. Co-treatment with a C1B5 domain peptide of protein kinase Cγ and a low dose of gemcitabine effectively inhibited pancreatic cancer growth in mouse peritoneal cavity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1107. doi:10.1158/1538-7445.AM2017-1107