Abstract
Despite enormous scientific advancements in cancer treatment, there is still so much to do to combat cancer particularly bladder cancer. Drugs once proved to be effective in treating bladder cancer showed reduced efficacy, hence, cancer recurrence rate is increasing. To overcome this situation, several attempts have been considered such as the development of a new effective drug or modify therapeutic regimens by combining two or more existing drugs. In recent years, atypical protein kinase C (aPKC), a phospholipid-dependent serine/threonine kinase, is considered as a central regulator of various cancer-causing signaling pathways and controls cell cycle progression, tumorigenesis, and metastatic determinant. In addition, the biologically important mammalian target of rapamycin (mTOR) pathway is altered in many cancers including bladder and can stimulate the activation of the aPKC pathway. In this study, we examined whether the concurrent inhibition of aPKC and mTOR using a combination of a novel aPKC inhibitor (ICA-I, an inhibitor of PKC-ι, or ζ-Stat, an inhibitor of PKC-ζ) and rapamycin blocks bladder cancer progression. The cell lines tested were MC-SV-HUCT2 normal bladder and TCCSUP bladder cancer cells. Our observed data showed that the combination therapy induced a significant reduction of human bladder cancer cells’ viability, also, individual treatment of aPKC inhibitor and rapamycin brought a similar effect. Moreover, the concurrent inhibition of aPKC and mTOR retards the metastasis of bladder cancer cells. These findings indicate that the administration of aPKC inhibitor together with rapamycin would be a useful therapeutic option in treating bladder cancer.
Citation Format: S M Anisul Islam, Rekha S. Patel, Raja Reddy Bommareddy, Tracess P. Smalley, Mildred Acevedo-Duncan. Simultaneous inhibition of Atypical Protein Kinase-C and mTOR impedes bladder canSimultaneous inhibition of atypical protein kinase-C and mTOR impedes bladder cancer cell progression of bladder cancer cell progression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4290.
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