COMBINATION THERAPY OF CISPLATIN AND NANOCURCUMIN REDUCES PI3K EXPRESSION AND PROLIFERATION OF HeLa CELLS
Abstract
Kanker serviks merupakan salah satu penyebab utama kematian akibat kanker pada wanita, terutama di negara berkembang. Cisplatin adalah obat kemoterapi yang umum digunakan, tetapi penggunaannya dalam dosis tinggi sering menyebabkan efek samping toksik seperti kerusakan ginjal (nefrotoksisitas), yang dapat terjadi pada 25–33% pasien pada dosis 75–100 mg/m². Untuk mengurangi toksisitas dan meningkatkan efektivitas terapi, kombinasi cisplatin dengan senyawa alami seperti nanokurkumin mulai dikembangkan. Penelitian ini bertujuan untuk mengevaluasi potensi kombinasi cisplatin dan nanokurkumin dalam menghambat proliferasi dan menurunkan ekspresi PI3K pada sel kanker serviks HeLa. Penelitian ini menggunakan desain eksperimental dengan post-test only control group. Sel HeLa diberi perlakuan cisplatin (2,5 dan 5 µg/mL), nanokurkumin (100 µg/mL), serta kombinasi cisplatin 2,5 µg/mL dengan nanokurkumin (25, 50, dan 100 µg/mL). Evaluasi mencakup morfologi sel, uji viabilitas menggunakan CCK-8, dan analisis ekspresi PI3K menggunakan flow cytometry. Analisis statistik dilakukan dengan uji Kruskal-Wallis, dilanjutkan uji post hoc Dunn, dengan nilai signifikansi p < 0,05. Hasil menunjukkan bahwa kombinasi cisplatin 2,5 µg/mL dan nanokurkumin 100 µg/mL secara signifikan menurunkan viabilitas sel dibandingkan cisplatin 2,5 µg/mL saja (p = 0,035), serta memiliki efektivitas yang sebanding dengan cisplatin 5 µg/mL (p = 0,553). Penurunan ekspresi PI3K juga signifikan dibandingkan kontrol negatif (p = 0,000), cisplatin 2,5 µg/mL (p = 0,006), dan cisplatin 5 µg/mL (p = 0,010). Hasil ini menunjukkan bahwa kombinasi cisplatin dan nanokurkumin berpotensi sebagai terapi kanker serviks yang efektif.
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References
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14. Cheng Y, Zhao P, Wu S, et al. Cisplatin and curcumin co-loaded nano-liposomes for the treatment of hepatocellular carcinoma. Int J Pharm. 2018;545(1-2):261-273. doi:10.1016/j.ijpharm.2018.05.007
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3. WHO. Cervical cancer. March 5, 2024. Accessed April 30, 2025. https://www.who.int/news-room/fact-sheets/detail/cervical-cancer
4. Bzeipez RK, Fayyadh SA. Impact of Cervical Cancer on Women’s Bio-Psycho-Social Aspects of Health: A Mixed Methods Study. Pakistan Journal of Medical & Health Sciences. 2022;16(06):668-668. doi:10.53350/PJMHS22166668
5. Nguyen VT, Winterman S, Playe M, et al. Dose-Intense Cisplatin-Based Neoadjuvant Chemotherapy Increases Survival in Advanced Cervical Cancer: An Up-to-Date Meta-Analysis. Cancers (Basel). 2022;14(3):842. doi:10.3390/CANCERS14030842/S1
6. Federico C, Sun J, Muz B, et al. Localized Delivery of Cisplatin to Cervical Cancer Improves Its Therapeutic Efficacy and Minimizes Its Side Effect Profile. International Journal of Radiation Oncology*Biology*Physics. 2021;109(5):1483-1494. doi:10.1016/J.IJROBP.2020.11.052
7. Elmorsy EA, Saber S, Hamad RS, et al. Advances in understanding cisplatin-induced toxicity: Molecular mechanisms and protective strategies. European Journal of Pharmaceutical Sciences. 2024;203:106939. doi:10.1016/J.EJPS.2024.106939
8. Katke A, Nanda R, Thejaswini B, et al. Weekly vs. tri-weekly cisplatin based chemoradiation in carcinoma cervix: a prospective randomized study of toxicity and compliance. Reports of Practical Oncology and Radiotherapy. 2021;26(6):948. doi:10.5603/RPOR.A2021.0115
9. Crona DJ, Faso A, Nishijima TF, McGraw KA, Galsky MD, Milowsky MI. A Systematic Review of Strategies to Prevent Cisplatin‐Induced Nephrotoxicity. Oncologist. 2017;22(5):609. doi:10.1634/THEONCOLOGIST.2016-0319
10. Zoi V, Galani V, Lianos GD, Voulgaris S, Kyritsis AP, Alexiou GA. The Role of Curcumin in Cancer Treatment. Biomedicines 2021, Vol 9, Page 1086. 2021;9(9):1086. doi:10.3390/BIOMEDICINES9091086
11. Stohs SJ, Chen O, Ray SD, Ji J, Bucci LR, Preuss HG. Highly Bioavailable Forms of Curcumin and Promising Avenues for Curcumin-Based Research and Application: A Review. Molecules 2020, Vol 25, Page 1397. 2020;25(6):1397. doi:10.3390/MOLECULES25061397
12. Hegde M, Girisa S, BharathwajChetty B, Vishwa R, Kunnumakkara AB. Curcumin Formulations for Better Bioavailability: What We Learned from Clinical Trials Thus Far? ACS Omega. 2023;8(12):10713-10746. doi:10.1021/ACSOMEGA.2C07326/ASSET/IMAGES/LARGE/AO2C07326_0003.JPEG
13. Rapti E, Adamantidi T, Efthymiopoulos P, Kyzas GZ, Tsoupras A. Potential Applications of the Anti-Inflammatory, Antithrombotic and Antioxidant Health-Promoting Properties of Curcumin: A Critical Review. Nutraceuticals 2024, Vol 4, Pages 562-595. 2024;4(4):562-595. doi:10.3390/NUTRACEUTICALS4040031
14. Cheng Y, Zhao P, Wu S, et al. Cisplatin and curcumin co-loaded nano-liposomes for the treatment of hepatocellular carcinoma. Int J Pharm. 2018;545(1-2):261-273. doi:10.1016/j.ijpharm.2018.05.007
15. Zhang L, Wu J, Ling MT, Zhao L, Zhao KN. The role of the PI3K/Akt/mTOR signalling pathway in human cancers induced by infection with human papillomaviruses. Mol Cancer. 2015;14(1):1-13. doi:10.1186/S12943-015-0361-X/FIGURES/2
16. Aldahoun MA, Jaafar MS, Al-Akhras MAH, Bououdina M. Enhanced nanocurcumin toxicity against (PC3) tumor and microbial by using magnetic field in vitro. Artif Cells Nanomed Biotechnol. 2017;45(4):843-853. doi:10.1080/21691401.2016.1178137
17. Becit M, Aydın Dilsiz S, Başaran N. Interaction of curcumin on cisplatin cytotoxicity in HeLa and HepG2 carcinoma cells. İstanbul Journal of Pharmacy. 2020;50(3). doi:10.26650/ISTANBULJPHARM.2020.0039
18. Kamiloglu S, Sari G, Ozdal T, Capanoglu E. Guidelines for cell viability assays. Food Front. 2020;1(3):332-349. doi:10.1002/FFT2.44;WEBSITE:WEBSITE:IADNS;CSUBTYPE:STRING:SPECIAL;PAGE:STRING:ARTICLE/CHAPTER
19. Mir MA, Sofi S. Cell Cycle and Cancer. Therapeutic potential of Cell Cycle Kinases in Breast Cancer. Published online January 1, 2023:83-101. doi:10.1007/978-981-19-8911-7_4
20. Prishya AAS, Chopra L, Manikanika, et al. Application of cisplatin and other platinum-containing drugs in cancer therapy: Comprehensive review. E3S Web of Conferences. 2024;588:02015. doi:10.1051/E3SCONF/202458802015
21. Varaprasad K, Sisubalan N, Jayaramudu T, Yallapu MM. Nanocurcumin: A new and improved way to fight cancer and infections. Nano-Structures & Nano-Objects. 2024;40:101352. doi:10.1016/J.NANOSO.2024.101352
22. Zhao X, Zhang R, Song Z, et al. Curcumin suppressed the proliferation and apoptosis of HPV-positive cervical cancer cells by directly targeting the E6 protein. Phytotherapy Research. 2023;38(10):4967-4981. doi:10.1002/PTR.7868;CSUBTYPE:STRING:SPECIAL;PAGE:STRING:ARTICLE/CHAPTER
23. Hafez Ghoran S, Calcaterra A, Abbasi M, Taktaz F, Nieselt K, Babaei E. Curcumin-Based Nanoformulations: A Promising Adjuvant towards Cancer Treatment. Molecules 2022, Vol 27, Page 5236. 2022;27(16):5236. doi:10.3390/MOLECULES27165236
24. Paul S, Sa G. Curcumin as an Adjuvant to Cancer Immunotherapy. Front Oncol. 2021;11:675923. doi:10.3389/FONC.2021.675923/XML/NLM
25. Hegde M, Kumar A, Girisa S, et al. Nanoformulations of curcumin: An alliance for effective cancer therapeutics. Food Biosci. 2023;56:103095. doi:10.1016/J.FBIO.2023.103095
26. Alavian F, Ghiasvand S. D S A D D A S D Systematic Review Effectiveness of Curcumin as a Low-cost Adjuvant Alternative to Vaccines in the Treatment of Human Papillomavirus-induced Cervical Cancer: A Systematic Review of In vitro and In vivo Studies. J Appl Biotechnol Rep. 2025;12(1):1517-1527. doi:10.30491/jabr.2024.455865.1728
27. Purbadi S, Yusuf M, Arozal W, et al. Antiproliferation and Apoptosis Effect of Cisplatin and Nanocurcumin on Ovarian Cancer SKOV3 Cell. Bali Medical Journal. 2022;11(1):377-381. doi:10.15562/BMJ.V11I1.2937
28. Subandi, Purbadi S. Effect of Nanocurcumin in Combination with Methotrexate on Telomerase Activity, NF-kb Expression, and Proliferation Index of Bewo Choriocarcinoma Cells: Indonesian Journal of Obstetrics and Gynecology. 2023;11(2):105-111. doi:10.32771/INAJOG.V11I2.1733
29. Boroughani M, Moaveni AK, Hatami P, et al. Nanocurcumin in cancer treatment: a comprehensive systematic review. Discover Oncology. 2024;15(1):1-32. doi:10.1007/S12672-024-01272-X/TABLES/4
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Authors
Subandi, S., Febriana, R., Taqiyya, N. ., & Endharti, A. T. (2025). COMBINATION THERAPY OF CISPLATIN AND NANOCURCUMIN REDUCES PI3K EXPRESSION AND PROLIFERATION OF HeLa CELLS. JURNAL RISET KESEHATAN POLTEKKES DEPKES BANDUNG, 17(2), 487–498. https://doi.org/10.34011/juriskesbdg.v17i2.2912
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