• 대한간호학회지
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• 제44권4호
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• pp.371-380
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• 2014

Purpose: The purpose of this study was to examine the effects of Cu/Zn SOD on reduction of hindlimb muscular atrophy induced by cisplatin in rats. Methods: Forty-two rats were assigned to three groups; control group, Cisplatin (CDDP) group and cisplatin with Cu/Zn SOD (CDDP-SOD) group. At day 35 hindlimb muscles were dissected. Food intake, activity, withdrawal threshold, muscle weight, and Type I, II fiber cross-sectional area (CSA) of dissected muscles were measured. Relative SOD activity and expression of MHC and phosphorylated Akt, ERK were measured after dissection. Results: Muscle weight and Type I, II fiber CSA of hindlimb muscles in the CDDP group were significantly less than the control group. Muscle weight and Type I, II fiber CSA of hindlimb muscles, food intake, activity, and withdrawal thresholds of the CDDP-SOD group were significantly greater than the CDDP group. There were no significant differences in relative SOD activities of hindlimb muscles between the CDDP-SOD and CDDP groups. MHC expression and phosphorylated Akt, ERK of hindlimb muscles in the CDDP-SOD group were significantly greater than the CDDP group. Conclusion: Cu/Zn SOD attenuates hindlimb muscular atrophy induced by cisplatin through increased food intake and activity. Increment of phosphorylated Akt, ERK may relate to attenuation of hindlimb muscular atrophy.

• Journal of Korean Biological Nursing Science
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• 제14권1호
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• pp.49-56
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• 2012

Purpose: The purpose of this study was to compare the effects of anorexia induced by consecutive low-dose and high-dose of cisplatin (CDDP) on the hindlimb muscles of rats. Methods: Male Sprague-Dawley rats were assigned to three groups: Control group (C) received a saline (the same dose and duration as the low CDDP group), the high-dose cisplatin (High CDDP) group received a single 5 mg/kg dose of cisplatin, the consecutive low-dose cisplatin (Low CDDP) group had 1 mg/kg of cisplatin administered for five consecutive days. On the 8th day the soleus and gastrocnemius muscles were dissected. Body weight, food intake, activity, muscle weight, Type I, II fiber cross-sectional area (CSA) of the dissected muscles were measured. Results: Body weight, food intake, muscle weight and Type I, II fiber CSA of the High CDDP and Low CDDP groups were significantly less than the C group. The High CDDP group showed significant decreases, compared to the Low CDDP group, in body weight, food intake, activity score, muscle weight and Type I, II fiber CSA. Conclusion: Hindlimb muscle atrophy occurs due to anorexia induced by both consecutive low-dose and high-dose cisplatin. The muscle atrophy induced by consecutive low-dose cisplatin is less apparent than high-dose cisplatin.

• Biomolecules & Therapeutics
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• 제12권2호
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• pp.85-91
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• 2004

In all attempt to elucidate the role of apoptosis in drug resistance, cisplatin-resistant human chronic myelogenous leukemia (CML) K562 cells (K562/CDDP) were established and compared with drug sensitive parent cells (K562) in the induction of apoptosis. K562/CDDP cells were 5-fold more resistant to cisplatin compared to K562 cells. In addition, K562/CDDP cells were significantly more resistant to apoptois as judged by DNA fragmentation and DAPI staining. K562/CDDP cells exhibited decreased proleolytic activity of caspase-3 and this was further demonstrated by decreased cleavage of its substrate poly (ADP-ribose) polymerase (PARR- Western blot analysis showed that K562/CDDP cells had longer sustained levels of BCL-$X_L$ whereas no difference was noted in the level of Bcl-2. the translocation of Bax to mitochondria was significantly delayed in K562/CDDP cells. These results suggest that the reduced translocation of Bax and the sustained expression of BCL-$X_L$ may cause resistance to apoptosis through prevention of mitochondria release of cytochrome c, which subsequently induces reduction of caspase-3 activity and that this response is partly responsible for the acquired resistance to cisplatin ill K562 cells.

• 대한의생명과학회지
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• 제14권2호
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• pp.83-89
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• 2008

We have compared the antitumor effect of photodynamic therapy (PDT), using 5-aminolevulinic acid (ALA) as the photosensitizer, combined with cisplatin (CDDP) on AMC-HN3 human squamous cell carcinoma. AMC-HN3 cells were cultured and then incubated with various concentrations of CDDP and ALA. 632 nm diode laser was given at $6.0J/cm^2$ followed by incubation for 24 hours. The evaluation of cell viability was done by MTT assay. In vivo CDDP was injected intraperitoneally 24 hours prior to PDT. The anti-tumor effects of each treatment were measured by tumor volume change. Cell viability were 44.29% for the cisplatin-mediated chemotherapy group $(6.25{\mu}g/ml)$, 77.22% for ALA-PDT group, and 15.06% for the Combination therapy group. In vivo, the antitumor effect of photodynamic therapy was enhanced by combination of Cisplatin-mediated chemotherapy. Photodynamic therapy combined with administration of Cisplatin appears to enhance antitumor effect and to be a useful treatment modality.

• BMB Reports
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• 제44권3호
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• pp.211-216
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• 2011

Vitamin C (VC) is an important antioxidant and enzyme co-factor that works by stimulating the immune system and protecting against infections. It is well known that melanoma cells are more susceptible to VC than any other tumor cells. However, the role of VC in the treatment of colon cancer has not been studied. Cisplatin (CDDP) is a DNA damaging agent and is widely used for treating cancer, while the role of p53 in CDDP-induced cell death has been stressed. Using cell growth assays, morphological methods, Western blotting, flow cytometry, and DNA fragmentation analysis, we measured the expression of p53 level involved in the effect of VC on CDDP-induced apoptosis of HCT116, a human colon cancer cell line. CDDP plus VC treatment resulted in significantly increased apoptosis along with upregulation of p53 compared to untreated cells and/or CDDP-treated cells. These results suggest that VC enhanced CDDP sensitivity and apoptosis via upregulation of p53.

• Applied Microscopy
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• 제40권3호
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• pp.133-138
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• 2010

인체 자궁암 세포 HeLa에 항암제 cisplatin (CDDP)과 산삼배양근 추출물(ETCMG)을 투여하여 세포 성장률, 형태, 전기영동에 의한 DNA fragmentation, 세포주기 분석을 통하여 apoptosis 유도를 확인하였다. ETCMG 2, 4, 6mg/mL, CDDP $4{\mu}g/mL$의 농도로 24시간 투여한 후 세포의 성장에 미치는 영향을 분석하고, ETCMG를 항암제로서 효과가 입증되어있는 CDDP와 복합투여하여 비교한 결과 apoptosis비율은 대조군에 비하여 ETCMG의 농도가 증가할수록 농도에 비례하여 현저히 증가하였고 (p<0.05), CDDP와 ETCMG를 복합투여한 경우에 ETCMG를 단독으로 투여한 경우 보다 apoptosis비율이 매우 높은것으로 나타났다(p<0.05). 세포의 형태를 도립현미경과 투과전자현미경으로 관찰한 결과, 대조군은 세포의 정상적인 형태를 유지하고 있는 반면에 CDDP와 ETCMG를 각각 처리한 암세포는 세포의 성장이 현저히 억제되었고, 염색질의 응축과 apoptotic body가 관찰되었다. 세포의 성장억제가 apoptosis에 의한 것인지를 확인하고자 DNA를 분리하여 전기영동한 결과, HeLa 세포에서 ETCMG의 농도가 증가할수록 ladder가 뚜렷이 관찰되었고, CDDP를 복합 처리한 것 역시 ETCMG의 농도에 비례하여 ladder가 선명하게 나타났다. Flow cytometry (FC)에 의한 세포주기 분석 결과, ETCMG를 농도별로 처리한 경우에 apoptosis를 나타내는 Sub-$G_1$기의 양이 농도에 비례하여 증가하였고, 항암제인 CDDP와 복합 투여한 경우에 Sub-$G_1$기 DNA양이 눈에 띠게 증가한 것으로 나타났다. 이상의 실험 결과를 종합하면, ETCMG는 인체 자궁암에서 항암효과를 가지고 있으며, 항암제 CDDP의 단독 투여보다는 ETCMG와 함께 사용하는 경우에 암 치료제로서의 상승효과가 있는 것으로 사료된다.

• BMB Reports
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• 제39권6호
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• pp.656-661
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• 2006

Cisplatin (CDDP) is a widely used anticancer drug, but at high dose, it can produce undesirable side effects such as hepatotoxicity. Because silymrin has been used to treat liver disorders, the protective effect of silymarin on CDDP -induced hepatotoxicity was evaluated in rats. Hepatotoxicity was determined by changes in serum alanine aminotransferase [ALT] and aspartate aminotransferase [AST], nitric oxide [NO] levels, albumin and calcium levels, and superoxide dismutase [SOD], glutathione peroxidase [GSHPx] activities, glutathione content, malondialdehyde [MDA] and nitric oxide [NO] levels in liver tissue of rats. Male albino rats were divided into four groups, 10 rats in each. In the control group, rats were injected i.p. with 0.2 ml of propylene glycol in saline 75/25 (v/v) for 5 consecutive days [Silymarin was dissolved in 0.2 ml of propylene glycol in saline 75/25 v/v]. The second group were injected with CDDP (7.5 mg /kg, I.P.), whereas animals in the third group were i.p. injected with silymarin at a dose of 100 mg/kg/day for 5 consecutive days. The Fourth group received a daily i.p. injection of silymarin (100 mg/kg/day for 5 days) 1 hr before a single i.p. injection of CDDP (7.5 mg/kg). CDDP hepatotoxicity was manifested biochemically by an increase in serum ALT and AST, elevation of MDA and NO in liver tissues as well as a decrease in GSH and the activities of antioxidant enzymes, including SOD, GSHPx in liver tissues. In addition, marked decrease in serum NO, albumin and calcium levels were observed. Serum ALT, AST, liver NO level, MDA was found to decreased in the combination group in comparison with the CDDP group. The activities of SOD, GSHPx, GSH and serum NO were lower in CDDP group than both the control and CDDP pretreated with silymarin groups. The results obtained suggested that silymarin significantly attenuated the hepatotoxicity as an indirect target of CDDP in an animal model of CDDP-induced nephrotoxicity.

• Asian Pacific Journal of Cancer Prevention
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• 제16권16호
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• pp.6877-6882
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• 2015

Background: Cisplatin (CDDP) is one of the most active cytotoxic agents in the treatment of cancer. We investigated the effect of selenium (Se) with high dose vitamin E (VE) administration to prevent CDDP-induced nephrotoxicity in rats. Materials and Methods: In this study, 40 female Wistar rats were randomly divided into five equal groups. The first group, which served as the control, was administered physiological saline (2.5 cc/day, 5 days) intraperitoneally (IP), while group A was administered cisplatin (6 mg/kg BW/ single dose) plus physiological saline IP. Groups B, C, D received IP five doses of Se (1.5 mg/kg BW), and a high dose of VE (1000 mg/kg BW) (Se-VE) in combination before, simultaneously, and after CDDP, respectively. The rats were sacrificed five days after CDDP administration. Plasma malondialdehide (MDA), glutathione peroxidase (GSH-Px), reduced glutathione (GSH), catalase, urea, creatinine levels, renal histopathological changes were measured. Results: The histopathological injury score, plasma levels of MDA, urea, creatinine were found to increase in group A compared to the control (p<0.05), while plasma levels of GSH-Px, GSH and catalase decreased (p<0.05). In contrast, plasma levels of MDA decreased (p<0.05) in groups B, C, D, which were treated with Se- VE, whereas levels of GSH-Px, GSH were found to increase only for group D (p<0.05). Plasma urea, creatinine levels improved in the treatment groups compared to group A (p<0.001). Histopathological changes caused by CDDP were also significantly improved after Se-VE treatment (p<0.05). Conclusions: Oxidative stress increases with CDDP-induced nephrotoxicity in rats. Se-VE supplementation might thus play a role in the prevention of CDDP-induced nephrotoxicity in patients.

• Molecules and Cells
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• 제37권9호
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• pp.699-704
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• 2014

Themetastasis-associated gene 1 (MTA1) oncogene hasbeen suggested to be involved in the regulation of cancer progression. However, there is still no direct evidence that MTA1 regulates cisplatin (CDDP) resistance, as well as cancer stem cell properties. In this study, we found that MTA1 was enriched in CNE1/CDDP cells. Knock down of MTA1 in CNE1/CDDP cells reversed CSCs properties and CDDP resistance. However, ectopic expression of MTA1 in CNE1 cells induced CSCs phenotypes and CDDP insensitivity. Interestingly, ectopic overexpression of MTA1-induced CSCs properties and CDDP resistance were reversed in CNE1 cells after inhibition of PI3K/Akt by LY294002. In addition, MTA1 expression and Akt activity in CNE1/CDDP cells was much higher than that in CNE1 cells. These results suggested that MTA1 may play a critical role in promoting CDDP resistance in NPC cells by regulatingcancer stem cell properties via thePI3K/Akt signaling pathway. Our findings suggested that MTA1 may be a potential target for overcoming CDDP resistance in NPC therapy.

• 대한임상검사과학회지
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• 제52권1호
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• pp.62-68
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• 2020

Cisplatin (CDDP)은 난소암 치료에 사용되는 화학 요법제로 암세포에 따라 그리고 치료 용량에 따라 다중 신호경로를 활성화하여 세포 반응을 다르게 일으킬 수 있다. Cisplatin이 세포에 작용하는 신호전달 기전은 분명하지 않아 더 많은 연구가 필요해 보인다. 이에 본 연구는 cisplatin을 난소암 세포(SKOV3)에 처리하여 세포사멸 유도 과정에서 나타나는 신호 단백질의 역할을 밝히고자 하였다. 결과는 cisplatin으로 처리한 난소암 세포에서 TUNEL assay와 유세포 분석을 통해 대조군과 비교하여 세포 사멸수가 증가하였다. 세포 사멸 단계에서 나타나는 PARP 및 caspase-3 활성도 증가하였다. 그러나 Bcl-2의 발현은 감소하였다. 신호 전달 경로에서 나타나는 단백질의 발현은 ERK1/2의 활성은 시간 의존적으로 감소하였으나 Akt 활성은 24시간에 감소하다 48시간에서의 활성은 일정하였다. p38과 p-JUN의 활성은 24시간에 증가하는 것으로 나타났으나 48시간에서 p38의 활성은 감소하였으며 p-JUN의 활성은 일정하였다. 이상의 결과들을 토대로 결론은 cisplatin이 SKOV3 세포에서 Akt 활성을 감소하여 세포 증식을 억제하고 MAPK의 p38 발현을 조절하여 세포사멸을 유도하는 것으로 판단된다. 향후, 암치료 전략에 도움이 되는 cisplatin을 포함한 백금기반 화학요법제의 신호전달 기전을 밝히기 위한 더 많은 연구가 필요할 것으로 생각된다. 본 실험을 통해 제시한 결과는 MAPK 신호 경로를 타겟으로 하는 암 치료 전략에 유용하게 사용 될 수 있기를 기대한다.