Cichoń Tomasz, Smolarczyk Ryszard, Matuszczak Sybilla, Barczyk Magdalena, Jarosz Magdalena, Szala Stanisław
Center for Translational Research and Molecular Biology of Cancer, Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Wybrzeże Armii Krajowej 15, 44-101, Gliwice, Poland,
Arch Immunol Ther Exp (Warsz). 2014 Aug;62(4):341-51. doi: 10.1007/s00005-014-0268-z. Epub 2014 Feb 2.
D-K6L9 peptide is bound by phosphatidylserine and induces necrosis in cancer cells. In our therapeutic experience, this peptide, when administered directly into B16-F10 murine melanoma tumors, inhibited their growth. Cessation of therapy results, however, in tumor relapse. We aimed at developing a combined therapy involving D-K6L9 and additional factors that would yield complete elimination of tumor cells in experimental animals. To this purpose, we employed glycyrrhizin, an inhibitor of HMGB1 protein, BP1 peptide and interleukin (IL)-12. Glycyrrhizin or BP1, when combined with D-K6L9, inhibits growth of primary tumors only during the period of their administration. A long-term tumor growth inhibitory effect was obtained only in combining D-K6L9 with IL-12. At 2 months following therapy cessation, 60 % of animals were alive. Prolonged survival was noted in mice bearing B16-F10 tumors as well as in mice bearing C26 colon carcinoma tumors.
D-K6L9肽与磷脂酰丝氨酸结合并诱导癌细胞坏死。根据我们的治疗经验，将这种肽直接注射到B16-F10小鼠黑色素瘤肿瘤中可抑制其生长。然而，停止治疗会导致肿瘤复发。我们旨在开发一种联合疗法，包括D-K6L9和其他能够在实验动物中完全消除肿瘤细胞的因素。为此，我们使用了甘草酸、HMGB1蛋白抑制剂、BP1肽和白细胞介素（IL）-12。甘草酸或BP1与D-K6L9联合使用时，仅在给药期间抑制原发性肿瘤的生长。只有将D-K6L9与IL-12联合使用才能获得长期的肿瘤生长抑制效果。在停止治疗2个月后，60%的动物存活。携带B16-F10肿瘤的小鼠以及携带C26结肠癌肿瘤的小鼠均出现了生存期延长的情况。
