title: A novel inhibitor of Rho GDP-dissociation inhibitor α improves the therapeutic efficacy of paclitaxel in Lewis lung carcinoma.
abstract: Molecular-targeted therapies are considered a promising strategy for the treatment of most types of human cancer. Rho GDP-dissociation inhibitor α (RhoGDIα), which functions mainly by controlling the cellular distribution and activity of Rho GTPases and is associated with tumor progression and poor prognosis of cancer patients, has become a new promising target for anticancer treatment. Recently, a specific RhoGDIα inhibitor (no. SKLB-163) was developed via computer-aided drug design andde novosynthesis. Previous studies have shown that SKLB-163 had extremely good antitumor activities against diverse cancer cell lines. In the present study, SKLB-163 was used in combination with paclitaxel in order to determine the synergistic effect of the antitumor activity. The findings showed that the combination therapy clearly inhibited cell proliferation and induced apoptosis of LL/2in vitro. The LL/2 mice model also showed that the combination therapy inhibited tumor growthin vivo. Proliferative cell nuclear antigen (PCNA) immunohistochmeistry and terminal deoxynucleotidyl transferase dUTP nick end-labeling showed that combination therapy inhibited cell proliferation and increased apoptosis compared to the treatment with SKLB-163 or paclitaxel alone. The data suggests that the combination therapy exerted synergistic antitumor effects, providing a novel way to augment the antitumor efficacy of cytotoxic chemotherapy.
authors.affiliation: Department of Medical Oncology, Cancer Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
authors.forename: Xing Chen
authors.initials: XC
authors.lastname: Peng
authors.affiliation: Department of Medical Oncology, Cancer Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
authors.forename: Xu Xia
authors.initials: XX
authors.lastname: Chen
authors.affiliation: Department of Oncology, Guizhou Provincial People's Hospital, Guiyang, Guizhou 550000, P.R. China.
authors.forename: Y U
authors.initials: YU
authors.lastname: Zhang
authors.affiliation: Department of Thoracic Surgery, Sichuan Cancer Hospital, Chengdu, Sichuan 610041, P.R. China.
authors.forename: Hai Jun
authors.initials: HJ
authors.lastname: Wang
authors.affiliation: Department of Medical Oncology, Cancer Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
authors.forename: You
authors.initials: Y
authors.lastname: Feng
keywords: Rho GDP-dissociation inhibitor α; apoptosis; molecular-targeted therapy; paclitaxel; proliferation