We investigated the effects of the anti-epilepsy drug valproic acid (VPA) alone and in combination in treating cervical cancer. VPA was investigated for its effects on cervical cancer Hela cell proliferation and tumor growth via in vitro and in vivo assays. 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. 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.
[1]Tulane Hlth Sci Ctr, Dept Med, Peptide Res Labs, New Orleans, LA 70112 USA.
[2]Louisiana State Univ, Hlth Sci Ctr, Sch Med, Dept Pathol, New Orleans, LA 70112 USA.
[3]Fudan Univ, Inst Genet, Sch Life Sci, State Key Lab Genet Engn, Shanghai 200433, Peoples R China.
[4]Beijing Univ Chem & Technol, Coll Life Sci & Technol, Beijing 100029, Peoples R China.
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