Abstract
BACKGROUND: Ovarian cancer is the fifth-most common female cancer and third-most common cancer in Indonesia, but most are advanced-stage patients that experiencing recurrence, which indicates resistance to treatment, especially to cisplatin. Melatonin appears as an alternative that can support the apoptotic effect of cisplatin as a chemotherapy regimen.AIM: To determine the effect of the combination of melatonin and cisplatin compared with cisplatin only chemotherapy on chemotherapy resistance with Copper-Transporting ATPase-1 (CTR-1), P-glycoprotein (P-Gp), and gamma-glutamylcysteinylglycine (GSH) biomarkers in ovarian cancer biological cells SKOV3.
METHODS: This research design was an experimental laboratory, posttest only control group design, using SKOV3 cell culture. This study was performed in the Stem Cells and Tissues Engineering Research Cluster IMERI FKUI laboratory and Integrated Laboratory FKUI. MTS assay was used to calculate the IC50 of each material. The materials used were melatonin (concentration was 25, 50, 100, 200, 300 nM), cisplatin (concentration was 0.1, 0.5, 1, 2, 5 mM), and doxorubicin (concentration 10, 20, 40, 50, 80, 100, 200 μM). IC50 melatonin was 1841 mM, IC50 cisplatin was 117,5 μM, and IC50 doxorubicin was 14,72 μM. Samples were control negative group, IC50 doxorubicin as control positive, IC50 cisplatin, IC50 melatonin, combination group of melatonin and cisplatin were 1xIC50, ¾ × IC50, ½ × IC50, and ¼ x IC50. ANOVA and the Bonferroni test were used for the statistical test.
RESULTS: Based on data processing, IC50 of melatonin was 1841 mM, IC50 of doxorubicin was 14.72 μM, whereas IC50 of cisplatin was 117.5 μM. The mean expression of CTR-1 in the IC50 melatonin group was 15.77 ± 0.21 and in the IC50 cisplatin group was 10.87 ± 0.91, mean expression in the IC50 doxorubicin group was 30.33 ± 0.4. Meanwhile, the mean expression of CTR-1 in IC50 cisplatin was 7.37 ± 0.7, and in combination 1 group (1 x IC50 melatonin and 1 x IC50 cisplatin) was 19. 73 ± 1.0. 49. For P glycoprotein, mean expression in IC50 cisplatin was 16 ± 1.59, in IC50 melatonin group was 7.37 ± 0.21, in IC50 doxorubicin was 0, and in combination 1 group (1 × IC50 melatonin and 1 × IC50 cisplatin) was 6.7 ± 0.17. Last, in GSH, mean expression in the IC50 cisplatin group was 33.2 ± 0.87, in IC50 melatonin group was 12.57 ± 0.12, in the IC50 doxorubicin group was 1.33 ± 0.66, and in combination 1 group (1 × IC50 melatonin and 1 × IC50 cisplatin) was 11.7 3± 0.67. There was a significant difference of CTR-1 expression in combination 1 group, which was higher (19.73%), P-Gp expression in combination 1 group, which was lower (6.7%), and also GSH expression in combination 1 group was lower (11.73%) compared to other groups.
CONCLUSION: The group 1 combination of 1 × IC50 melatonin and 1 × IC50 cislatin with 1.841 mM and cisplatin 117.5 uM was able to reduce cisplatin chemotherapy resistance by increasing drug influx activity by increasing CTR-1 expression, decreasing drug efflux through decreasing P-Gp expression, and decreased DNA repair activity through decreased GSH expression
METHODS: This research design was an experimental laboratory, posttest only control group design, using SKOV3 cell culture. This study was performed in the Stem Cells and Tissues Engineering Research Cluster IMERI FKUI laboratory and Integrated Laboratory FKUI. MTS assay was used to calculate the IC50 of each material. The materials used were melatonin (concentration was 25, 50, 100, 200, 300 nM), cisplatin (concentration was 0.1, 0.5, 1, 2, 5 mM), and doxorubicin (concentration 10, 20, 40, 50, 80, 100, 200 μM). IC50 melatonin was 1841 mM, IC50 cisplatin was 117,5 μM, and IC50 doxorubicin was 14,72 μM. Samples were control negative group, IC50 doxorubicin as control positive, IC50 cisplatin, IC50 melatonin, combination group of melatonin and cisplatin were 1xIC50, ¾ × IC50, ½ × IC50, and ¼ x IC50. ANOVA and the Bonferroni test were used for the statistical test.
RESULTS: Based on data processing, IC50 of melatonin was 1841 mM, IC50 of doxorubicin was 14.72 μM, whereas IC50 of cisplatin was 117.5 μM. The mean expression of CTR-1 in the IC50 melatonin group was 15.77 ± 0.21 and in the IC50 cisplatin group was 10.87 ± 0.91, mean expression in the IC50 doxorubicin group was 30.33 ± 0.4. Meanwhile, the mean expression of CTR-1 in IC50 cisplatin was 7.37 ± 0.7, and in combination 1 group (1 x IC50 melatonin and 1 x IC50 cisplatin) was 19. 73 ± 1.0. 49. For P glycoprotein, mean expression in IC50 cisplatin was 16 ± 1.59, in IC50 melatonin group was 7.37 ± 0.21, in IC50 doxorubicin was 0, and in combination 1 group (1 × IC50 melatonin and 1 × IC50 cisplatin) was 6.7 ± 0.17. Last, in GSH, mean expression in the IC50 cisplatin group was 33.2 ± 0.87, in IC50 melatonin group was 12.57 ± 0.12, in the IC50 doxorubicin group was 1.33 ± 0.66, and in combination 1 group (1 × IC50 melatonin and 1 × IC50 cisplatin) was 11.7 3± 0.67. There was a significant difference of CTR-1 expression in combination 1 group, which was higher (19.73%), P-Gp expression in combination 1 group, which was lower (6.7%), and also GSH expression in combination 1 group was lower (11.73%) compared to other groups.
CONCLUSION: The group 1 combination of 1 × IC50 melatonin and 1 × IC50 cislatin with 1.841 mM and cisplatin 117.5 uM was able to reduce cisplatin chemotherapy resistance by increasing drug influx activity by increasing CTR-1 expression, decreasing drug efflux through decreasing P-Gp expression, and decreased DNA repair activity through decreased GSH expression
| Original language | English |
|---|---|
| Journal | Open Access Macedonian Journal of Medical Sciences |
| Volume | 10 |
| DOIs | |
| Publication status | Published - 23 Apr 2022 |
