title: Tetraarsenic oxide and cisplatin induce apoptotic synergism in cervical             cancer.
abstract: Tetraarsenic oxide (As4O6, TAO) is a new arsenic compound that inhibits             cell growth and induces apoptosis in human cervical cancer cell lines. In the             present study, we report that the growth of tumor cells (CaSki) was inhibited             by treatment with TAO alone or in combination with cisplatin or paclitaxel in             vitro and in vivo. Proliferation was assessed by WST-1 assay, and apoptosis was             assessed by Annexin-V/PI FACS analysis in the CaSki cell line treated with a single             agent or with the combinations of two agents. Expression of apoptosis-related             proteins was analyzed by western blot analysis. A mouse xenograft model using             CaSki cells was used to determine the in vivo activity of tetraarsenic oxide alone             and in combination with cisplatin or paclitaxel by estimation of tumor size. At             the end of the experiment, tumor tissue from each mouse was removed and processed             for TUNEL analysis for confirmation of apoptotic cells. TAO was able to inhibit             cell proliferation in a time- and dose-dependent manner. A combination of TAO             and cisplatin effectively induced apoptosis by activating caspase-3. Using a mouse             xenograft model, the sizes of tumors which were treated with a single agent and             with a combination of agents decreased in a time-dependent manner. A combination             of TAO and cisplatin resulted in a significantly reduced tumor size (P<0.05).             The data for the histochemical staining of TUNEL-positive cells showed that the             number of apoptotic cells was significantly increased by the combination of TAO             and cisplatin. Thus, TAO is a good candidate for use in a combined regimen with             cisplatin for patients with cervical cancer.
authors: Department of Obstetrics and Gynecology, Busan Paik Hospital, Inje University, Busan 614-735, Republic of Korea.
authors: Jung Mi
authors: JM
authors: Byun
authors: Dae Hoon
authors: DH
authors: Jeong
authors: Dae Sim
authors: DS
authors: Lee
authors: Joo Ran
authors: JR
authors: Kim
authors: Sae Gwang
authors: SG
authors: Park
authors: Mi Seon
authors: MS
authors: Kang
authors: Young Nam
authors: YN
authors: Kim
authors: Kyung Bok
authors: KB
authors: Lee
authors: Moon Su
authors: MS
authors: Sung
authors: Ki Tae
authors: KT
authors: Kim
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000008:administration & dosage*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000008:administration & dosage*; D004357:Drug Synergism; D005260:Female; D006801:Humans; D051379:Mice; D010087:Oxides / Q000008:administration & dosage*; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000473:pathology; D023041:Xenograft Model Antitumor Assays
chemical_list: D001152:Arsenicals; D010087:Oxides; D002945:Cisplatin; D000077237:Arsenic Trioxide