1. Valproic acid suppresses cervical cancer tumor progression possibly via activating Notch1 signaling and enhances receptor-targeted cancer chemotherapeutic via activating somatostatin receptor type II.
- Author
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Tsai C, Leslie JS, Franko-Tobin LG, Prasnal MC, Yang T, Vienna Mackey L, Fuselier JA, Coy DH, Liu M, Yu C, and Sun L
- Subjects
- Animals, Cell Differentiation drug effects, Cell Proliferation drug effects, Colchicine therapeutic use, Cyclin-Dependent Kinase Inhibitor p21 genetics, Cyclooxygenase 2 metabolism, Drug Combinations, G2 Phase Cell Cycle Checkpoints drug effects, Gene Expression, Genes, p53 drug effects, HeLa Cells, Hormones therapeutic use, Humans, Membrane Proteins genetics, Mice, Mice, Nude, PTEN Phosphohydrolase metabolism, Phosphatidylinositol 3-Kinases metabolism, RNA, Messenger metabolism, Receptor, Notch1 genetics, Somatostatin therapeutic use, Tubulin Modulators therapeutic use, Anticonvulsants pharmacology, Carcinoma drug therapy, Receptor, Notch1 metabolism, Receptors, Somatostatin metabolism, Signal Transduction drug effects, Valproic Acid pharmacology
- Abstract
Purpose: We investigated the effects of the anti-epilepsy drug valproic acid (VPA) alone and in combination in treating cervical cancer., Methods: VPA was investigated for its effects on cervical cancer Hela cell proliferation and tumor growth via in vitro and in vivo assays., Results: VPA induce cell growth suppression and cell cycle arrest, with an increase of Notch1 that acts as a tumor suppressor and the change of other tumor-associated genes such as p21, p63 and PCNA. VPA was also found to induce cell morphological change, with an increase of certain cell transformation markers such as snail1, snail2 and N-cadherin. Moreover, VPA could significantly up-regulate somatostatin receptor type II (SSTR2). Our in vivo study further demonstrated that VPA via inducing SSTR2 up-regulation extremely enhanced the anti-tumor ability of the SSTR2-preferential cytotoxic COL-SST conjugate in xenografts., Conclusions: VPA could not only suppress tumor progression but also provide a novel promising therapeutic choice in combination with a receptor-targeted cytotoxic conjugate via activating the specific receptor.
- Published
- 2013
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