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5.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 45(4): 606-11, 2014 Jul.
Article in Chinese | MEDLINE | ID: mdl-25286685

ABSTRACT

OBJECTIVE: To investigate the effects and mechanisms of hyperthermia combined with various platinum-based drugs cis-platinum (DDP), carboplatin (CBP), oxaliplatin (OXA) on the proliferation and apoptosis of ovarian cancer cell lines SKOV3. METHODS: SKOV3 cells were treated with different concentrations of anticancer drugs DDP (final concentration respectively 0, 1.25, 2.5, 5.0, 10.0, 20.0 microg/mL), CBP and OXA (both final concentration respectively 0, 2.5, 5.0, 10.0, 20.0, 40 microg/mL) at a temperature of 42 degrees C for hyperthermia or 37 degrees C for normal temperature. Methyl thiazolyl tetrazolium (MTT) method was used to test growth ratios of ovarian cancer cell lines SKOV3. Real-time PCR was adopted to detect the expression level of excision repair cross-complementing group 1 (ERCC1) and Survivin mRNA in SKOV3 cells. RESULTS: DDP, CBP and OXA inhibited the growth of SKOV3 in a dose-dependent manner (P < 0.05). Hyperthermia could increase the sensitivity of SKOV3 to cis-platinum, carboplatin and oxaliplatin (P < 0.05). The half inhibitory concentration (IC50) values of DDP, CBP and OXA were (7.271 +/- 0.096) microg/mL, (37.609 +/- 0.779) microg/mL and (28.328 +/- 0.698) microg/mL respectively. When combined with hyperthermia, the IC50 values of DDP, CBP, and OXA were (2.075 +/- 0.244) microg/mL, (19.591 +/- 0.453) microg/mL, (19.089 +/- 0.424) microg/mL (P < 0.05). The increased sensitivity index was 2.075 +/- 0.244 for cis-platinum, 1.92 +/- 0.044 for carboplatin, 1.484 +/- 0.039 for oxaliplatin. After the treatment of hyperthermia, the expression of ERCC1 and Survivin mRNA showed downward trend. ERCC1 decreased more significantly in the group of hyperthermia combined with carboplatin, and Survivin decreased more significantly in the group of hyperthermia combined with oxaliplatin (P < 0.05). CONCLUSION: Hyperthermia can enhance the sensitivity of ovarian cancer SKOV3 cells to platinum-based drugs, which may be related to the down regulation of ERCC1 and Survivin expression.


Subject(s)
Antineoplastic Agents/pharmacology , Drug Resistance, Neoplasm , Hot Temperature , Ovarian Neoplasms/pathology , Platinum/pharmacology , Apoptosis , Carboplatin , Cell Line , Cell Line, Tumor/drug effects , Cell Proliferation , Cisplatin , DNA-Binding Proteins/metabolism , Down-Regulation , Endonucleases/metabolism , Female , Humans , Inhibitor of Apoptosis Proteins/metabolism , Organoplatinum Compounds , Oxaliplatin , RNA, Messenger , Survivin
6.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 45(4): 612-7, 2014 Jul.
Article in Chinese | MEDLINE | ID: mdl-25286686

ABSTRACT

OBJECTIVE: To investigate the expression level of chloride intracellular channel 1 (CLIC1) and insulin-like growth factor binding protein 7 (IGFBP7) in complete hydatidiform mole (CHM) and estimate the relationship between the expression level and clinical prognosis. METHODS: Immunohistochemistry (IHC) method was used to detect the expression level of P57(KIP2) in order to differentiate CHM. CLIC1 and IGFBP7 expression level of CHM were measured by IHC method then. RESULTS: (1) According to the P57(KIP2) expression result 66 patients were diagnosed as CHM (85.71%). Fourteen of 66 patients progressed into gestational trophoblastic neoplasia (GTN), which accounted for 21.21%. (2) The results of IHC showed that CLIC1 significantly higher expressed in malignant group than spontaneous regressive group (P = 0.014). IGFBP7 significantly down-regulated in malignant group (P = 0.002). (3) Pearson correlation analysis results revealed that there were no relation between the expression of CLIC1 and IGFBP7 (P = 0.761). Logistic regression analysis indicated that down-regulation of IGFBP7 was the independent risk factors of CHM progression, P = 0.005, OR = 8.493 (95% confidence interval (CI): 1.878-38.401); Serum hCG > 5 x 10(5) mIU/mL was the independent risk factors of CHM progression too, P = 0.011, OR = 11.251 (95% CI: 1.731-73.151). (4) Receiver operator characteristic curve (ROC curve) results showed that the area under the curve (AUC) of CLIC1 was 0.707. The optimum cut off was 10.5, and correspondingly sensitivity was 42.90%, specificity 94.20%. AUC of IGFBP7 was 0.764. The optimum cut off was 7.0, and the correspondingly sensitivity and specificity were 64.30% and 78.80% respectively. Combining the two markers in series, the sensitivity of predicting the prognosis of CHM was 21.42%, while the specificity was 100%. When combining in parallel, the sensitivity and specificity were 85.71% and 71.15% respectively. CONCLUSION: Up-regulation of CLIC1 and down-regulation of IGFBP7 might pay an important role in progression of CHM, but there was no relationship between the expression levels of them. The predictive values of malignance transformation of CHM with the two biomarkers were with certain accuracy, and combining them in parallel test could improve accuracy. They are promising to be candidate prognostic markers of CHM.


Subject(s)
Chloride Channels/metabolism , Hydatidiform Mole/metabolism , Insulin-Like Growth Factor Binding Proteins/metabolism , Uterine Neoplasms/metabolism , Chloride Channels/genetics , Disease Progression , Down-Regulation , Female , Gestational Trophoblastic Disease , Humans , Hydatidiform Mole/genetics , Immunohistochemistry , Insulin-Like Growth Factor Binding Proteins/genetics , Pregnancy , ROC Curve , Risk Factors , Sensitivity and Specificity , Up-Regulation , Uterine Neoplasms/genetics
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