시스플라틴은 지난 몇 십년간 가장 많이 사용되고 있는 항암제 중 하나이다. 2가의 시스플라틴의 가장 큰 단점은 암세포 뿐만 아니라 정상세포도 공격하여 부작용을 나타낸다. 본 연구에서는 이러한 단점을 줄이기 위해 목표로 한 타겟을 공격하여 빠른 시간 내에 암세포를 죽일 수 있는 4가의 백금화합물 3과 4를 합성하였다. 합성된 Pt(IV)-Bu2 3 and Pt(IV)-Val2 4는 NMR과 질량분석기를 통하여 구조를 확인 하였다. 합성된 Pt(IV) 화합물 3과 4는 위암세포주인 MCF-7을 대상으로 한 MTT assay를 통해 항암효과를 조사하였다. 그 결과 시스플라틴은 39%, Pt(IV)-Bu2 3와 Pt(IV-Val2 4는 50μM 농도에서 각각 54%와 84%의 세포사멸을 보였다.

Immunoprecipitation-based high performance liquid chromatography (IP-HPLC) is a type of modified enzyme-linked immunosorbent assay (ELISA) that uses protein A/G (or antibody)-conjugated beads instead of the antibody-conjugated wells used in ELISA. In order to determine the fidelity of IP-HPLC, the author used 83 antisera to identify protein expression changes caused by cisplatin treatment in KB human oral cancer cells. KB cells were cultured for 12 or 24 hours with 10 ug/mL cisplatin. The results obtained by IP-HPLC were comparable with published cisplatin data, although ELISA was not conducted in the present study. Cisplatin dominantly reduced the levels of proteins associated with cell proliferation, transcription factors, growth factors, cytoskeletal proteins, and cellular differentiating factors, but on the other hand, apoptosis-related factors, oncogenes, and protective proteins were usually up-regulated, presumably to address cisplatin-induced DNA damage. In particular, cisplatin directly inactivated genomic DNA by down-regulating histone H1 and demethylase and by up-regulating deacetylase. Cisplatin also rapidly induced p53 overexpression and mitochondria-mediated endogenous apoptosis occurred after 12 hours of cisplatin treatment, although this was almost completely replaced by FASL/FAS-mediated exogenous apoptosis after 24 hours. This preliminary study was conducted to investigate the anticancer effect of cisplatin on the KB human oral cancer cells and to determine the fidelity of IP-HPLC data. It was concluded that IP-HPLC is useful for identifying profile changes of genome wide essential proteins and signaling changes of major molecular pathways.

Photodynamic therapy(PDT) is recently developed as an effective treatment for malignant disease. Carboplatin, a less nephrotoxic analog of cisplatin, has been widely used for the treatment of multiple malignancies. In this study, we investigated the cytotoxic and apoptotic effect of combined modality of photofrin mediated PDT with cisplatin and carboplatin on KB cell human oral cancer cell line in vitro. The a ttached KB cells were incu bated with c isplatin(0.04mg/ml) and carboplatin(0.02mg/ml) for 24h at 37℃ and followed by photosensitization with photofrin for 6h and laser irradiation with 630nm LED at an intensity of 2.0 J/cm2 for activating photofrin for 15min. Then MTT assay and SYTO 16 green & Propidium iodide (PI) double staining were used respectively to measure the cytotoxicity and nuclear morphology at 24h after PDT. This study demonstrates that the combined modality with carbopaltin resulted in enhanced apoptotic cell death as well as cytotoxic e ffect on KB c ells in vitro, which s uggests the feasibility of combined modality and the possibility o f reducing the effective dosage of photofrin and carboplatin and lowering the side effects on normal cells

Background : In this study, we investigated the renoprotective effects of serotonin and its derivatives, on the renal function and expression of inflammation and apoptosis in cisplatin-induced nephrotoxicity mice. Methods and Results : Serotonin and its derivatives were orally administered at a dose of 7.5 mg/kg body weight for 5 days before the intraperitoneal injection of cisplatin 20 mg/kg body weight, and the effects were compared with those of vehicle-treated nephrotoxicity control and normal groups. In the serum and kidney, renal function parameters, reactive oxygen species and expression of protein related to pro-oxidant, antioxidant, inflammation and apoptosis were examined. As a result, serotonin and its derivatives administrations to nephrotoxicity mice lowered serum BUN and creatinine concentrations. These results were derived, at least in part, from attenuation the expression of antioxidant enzymes-related proteins, SOD and GPx. In the cisplatin-induced renal condition, augmented p-p38, p-ERK and p-JNK (mitogen-activated protein kinase pathway) were reduced with a increase in antioxidant enzymes on serotonin and its derivatives treatment. Moreover, in the serotonin and its derivatives-treated groups, NF- κB-induced inflammatory factors and apoptotic protein expressions were regulated in the kidney. Conclusion : The present study indicates that serotonin and its derivatives exerts a renoprotective effect against cisplatin-induced nephrotoxicity through the recovery of kidney function deterioration and attenuation of renal inflammation and apoptosis by regulating oxidative stress condition.