THE DIFFERENCES OF APOPTOSIS EFFECTS BETWEEN COMBINATION OF MELOXICAM WITH GEMCITABINE-CARBOPLATIN CHEMOTHERAPY COMPARED TO GEMCITABINE-CARBOPLATIN CHEMOTHERAPY ALONE IN UROTHELIAL CARCINOMA CULTURE CELLS

Ananta Cahyo Nugroho, Lukman Hakim, Wahjoe Dajtisoesanto, Doddy M Soebadi

Abstract


Objective: To determine the differences of apoptosis effect between the combination of meloxicam and gemcitabine-carboplatin compared to gemcitabine-carboplatin alone as the standard of chemotherapy care in urothelial carcinoma culture cells. Material & Methods: This research is an in vitro experimental using human bladder cell carcinoma type 5637 which was cultured in the laboratory. In this study, the study group was divided into 3 groups: untreated control group, gemcitabine-carboplatin group, and the meloxicam-gemcitabine-carboplatin combination group, each group consist of 5 replications. To determine the dose of meloxicam, gemcitabine, carboplatin used and the time of apoptosis evaluation, cytotoxic tests were carried out using the MTT assay method. The time of apoptosis evaluation is carried out for 24 hours. Apoptosis was assessed using the Apoptotag reagent from Trevigen®. Observation of apoptosis characterized by a positive reaction (the color turning brown) against DNA strand damage using the TUNEL assay method. One Way ANOVA was used for comparative analysis of apoptosis between the group with a significant value of p<0.05. The analysis was continued with a post hoc test, to determine the differences in each group. Results: The mean of apoptosis in the control group, gemcitabine-carboplatin group, apoptosis and the meloxicam-gemcitabine-carboplatin combination group was 0.748%, 80.336%, and 83.312%, respectively. Post hoc Bonferroni analysis showed that the results had significant difference between the meloxicam-gemcitabine-carboplatin combination group compared to the gemcitabine-carboplatin group (p=0.026) and the control group (p=0.000). Conclusion: Meloxicam-gemcitabine-carboplatin combination therapy has a significantly higher apoptotic effect than gemcitabine-carboplatin alone.


Keywords


Meloxicam; gemcitabine; carboplatin; apoptosis

Full Text:

PDF

References


Vrooman OPJ, Witjes JA. Urinary markers in bladder cancer. 2008; 53: 909–16.

Burger M, Catto JWF, Dalbagni G, Grossman HB, Herr H, Karakiewicz P, et al. Epidemiology and risk factors of urothelial bladder cancer. Eur Urol. 2013; 63(2): 234–41.

Ploeg M, Aben KKH, Kiemeney LA. The present and future burden of urinary bladder cancer in the world. World J Urol. 2009; 27(3): 289–93.

World Health Organization. Global Cancer: Society. 2008; (700): 1–57.

Umbas R, Safriadi F, Mochtar CA, Djatisoesanto W, Hamid ARAH. Urologic cancer in Indonesia. Jpn J Clin Oncol. 2015; 45(8): 708–12.

Babjuk M, Böhle A, Burger M, Capoun O, Cohen D, Compérat EM, et al. EAU guidelines on non–muscle-invasive urothelial carcinoma of the bladder: update 2016. Eur Urol. 2017; 71(3): 447–61.

Stenzl A, Cowan NC, Santis M De, Kuczyk MA, Merseburger AS, Jose M. Treatment of muscle-invasive and metastatic bladder cancer: update of the EAU guidelines. 2011; 59: 1009–18.

Leow JJ, Martin-doyle W, Rajagopal PS, Patel CG, Anderson EM, Rothman AT, et al. Adjuvant chemotherapy for invasive bladder cancer: a 2013 updated systematic review and meta-analysis of randomized trials. Eur Urol. 2014; 66(1): 42–54.

Maase H Von Der, Sengelov L, Roberts JT, Ricci S, Dogliotti L, Oliver T, et al. Long-term survival results of a randomized trial comparing gemcitabine plus cisplatin, with methotrexate, vinblastine, doxorubicin, plus cisplatin in patients with bladder cancer. 2005; 23(21).

Galsky MD, Chen GJ, Oh WK, Bellmunt J, Roth BJ, Petrioli R, et al. Comparative effectiveness of cisplatin-based and carboplatin-based chemotherapy for treatment of advanced urothelial carcinoma. Ann Oncol. 2012; 23(2): 406–10.

Costantini C, Millard F. Update on chemotherapy in the treatment of urothelial carcinoma; 2011. p. 1981–94.

Bamias A, Moulopoulos LA, Koutras A, Aravantinos G, Fountzilas G, Pectasides D, et al. The combination of gemcitabine and carboplatin as first-line treatment in patients with advanced urothelial carcinoma: A phase II study of the hellenic cooperative oncology group. Cancer. 2006; 106(2): 297–303.

De Nardi AB, Raposo TMM, Huppes RR, Daleck CR, Amorim RL. COX-2 inhibitors for cancer treatment in dogs. Pak Vet J. 2011; 31(4): 275–9.

O’Kane SL, Eagle GL, Greenman J, Lind MJ, Cawkwell L. COX-2 specific inhibitors enhance the cytotoxic effects of pemetrexed in mesothelioma cell lines. Lung Cancer. 2010; 67(2): 160–5.

Arantes-Rodrigues R, Pinto-Leite R, Ferreira R, Neuparth MJ, Pires MJ, Gaivão I, et al. Meloxicam in the treatment of in vitro and in vivo models of urinary bladder cancer. Biomed Pharmacother. 2013; 67(4): 277–84.

Yoon C, Lee HJ, Park DJ, Lee YJ, Tap WD, Eisinger-Mathason TSK, et al. Hypoxia-activated chemotherapeutic TH-302 enhances the effects of VEGF-A inhibition and radiation on sarcomas. Br J Cancer. 2015; 113(1): 46–56.

Stein JP, Lieskovsky G, Cote R, Groshen S, Feng A-C, Boyd S, et al. Radical cystectomy in the treatment of invasive bladder cancer: long-term results in 1.054 patients. J Clin Oncol [Internet]. 1st February 2001 [dikutip 30 Oktober 2018]; 19(3): 666–75. Tersedia pada: http://www.ncbi.nlm.nih.gov/pubmed/11157016

Liu CH, Chang SH, Narko K, Trifan OC, Wu MT, Smith E, et al. Overexpression of cyclooxygenase-2 is sufficient to induce tumorigenesis in transgenic mice. J Biol Chem. 2001; 276(21): 18563–9.

Chou T. Theoritical basis, experimental design, and computerized simulation of synergism and antagonism in drug combination studies. Pharmacol Rev. 2007; 58(3): 623–74.

Santos L, Amado F, Bernardo C, Costa C, Freitas R, Oliveira P, et al. What we have learned from urinary bladder cancer models. J Cancer Metastasis Treat. 2015; 2: 51–8.

Wang S, Zhang H, Cheng L, Evans C, Pan CX. Analysis of the cytotoxic activity of the carboplatin and gemcitabine combination. Anticancer Res. 2010; 30(11): 4573–8.

Goldstein JL, Silverstein FE, Agrawal NM, Hubbard RC, Kaiser J, Maurath CJ, et al. Reduced risk of upper gastrointestinal ulcer complications with celecoxib, a novel COX-2 inhibitor. Am J Gastroenterol. 2000; 95(7): 1681–90.

Labayle D, Fischer D, Vielh P, Drouhin F, Pariente A, Bories C, et al. Sulindac causes regression of rectal polyps in familial adenomatous polyposis. Gastroenterology. 1991; 101(3): 635–9.

Naruse T, Nishida Y, Ishiguro N. Synergistic effects of meloxicam and conventional cytotoxic drugs in human MG-63 osteosarcoma cells. Biomed Pharmacother. 2007; 61(6): 338–46.

Sabichi AL, Lippman SM. COX-2 inhibitors and other nonsteroidal anti-inflammatory drugs in genitourinary cancer. Semin Oncol. 2004; 31(Suppl. 7): 36–44.

Bommer N, Hayes A, Scase T, Gunn-Moore D. Clinical features, survival times and COX-1 and COX-2 expression in cats with transitional cell carcinoma of the urinary bladder treated with meloxicam. J Feline Med Surg. 2012; 14(8): 527–33.




DOI: http://dx.doi.org/10.32421/juri.v26i1.538

Refbacks

  • There are currently no refbacks.


Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

Index by: