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Co-treatment with Celecoxib or NS398 Strongly Sensitizes Resistant Cancer Cells to Antimitotic Drugs Independent of P-gp Inhibition.
Anticancer Res 2016; 36(10):5063-5070AR

Abstract

BACKGROUND/AIM

Inhibition of cyclooxygenase-2 (COX-2) has been investigated in clinical trials. Currently, NS398 and celecoxib are the most commonly used COX-2 inhibitors. The purpose of this study was to identify conditions that would increase the sensitivity of resistant cancer cells to antimitotic drugs.

MATERIALS AND METHODS

We tested whether COX-2 inhibitors can sensitize drug-resistant KBV20C cancer cells. We also compared the efficacy of NS398 with that of celecoxib.

RESULTS

Both NS398 and celecoxib could sensitize KB and KBV20C cells to a similar extent, suggesting that COX-2 inhibitors could be used for sensitive, as well as resistant, cancer cells. We demonstrated that the NS398 and celecoxib sensitization mechanism is independent of the inhibition of p-glycoprotein (P-gp), suggesting that resistant KBV20C cells are sensitized through targeting of signaling pathways by both drugs. Furthermore, through using microscopic observation, assessment of cleaved poly ADP ribose polymerase (C-PARP) and annexin V staining we determined that both COX-2 inhibitors strongly sensitized resistant KBV20C cells to vinblastine (VIB) or paclitaxel (PAC) treatment. These results suggest that antimitotic drug-resistant cancer cells can be strongly sensitized by co-treatment with COX-2 inhibitors, without P-gp inhibitory activity.

CONCLUSION

These findings provide important information regarding the sensitization of drug-resistant cells and indicate that COX-2 inhibitors may be used for potentially resistant cancer patients, without the toxic effects of P-gp inhibition.

Authors+Show Affiliations

School of Pharmacy, Sungkyunkwan University, Suwon, Republic of Korea.School of Pharmacy, Sungkyunkwan University, Suwon, Republic of Korea.School of Pharmacy, Sungkyunkwan University, Suwon, Republic of Korea.School of Pharmacy, Sungkyunkwan University, Suwon, Republic of Korea hkims@skku.edu syoon88@gmail.com.School of Pharmacy, Sungkyunkwan University, Suwon, Republic of Korea hkims@skku.edu syoon88@gmail.com.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

27798865

Citation

Lim, Jong Seung, et al. "Co-treatment With Celecoxib or NS398 Strongly Sensitizes Resistant Cancer Cells to Antimitotic Drugs Independent of P-gp Inhibition." Anticancer Research, vol. 36, no. 10, 2016, pp. 5063-5070.
Lim JS, Park Y, Lee BM, et al. Co-treatment with Celecoxib or NS398 Strongly Sensitizes Resistant Cancer Cells to Antimitotic Drugs Independent of P-gp Inhibition. Anticancer Res. 2016;36(10):5063-5070.
Lim, J. S., Park, Y., Lee, B. M., Kim, H. S., & Yoon, S. (2016). Co-treatment with Celecoxib or NS398 Strongly Sensitizes Resistant Cancer Cells to Antimitotic Drugs Independent of P-gp Inhibition. Anticancer Research, 36(10), pp. 5063-5070.
Lim JS, et al. Co-treatment With Celecoxib or NS398 Strongly Sensitizes Resistant Cancer Cells to Antimitotic Drugs Independent of P-gp Inhibition. Anticancer Res. 2016;36(10):5063-5070. PubMed PMID: 27798865.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Co-treatment with Celecoxib or NS398 Strongly Sensitizes Resistant Cancer Cells to Antimitotic Drugs Independent of P-gp Inhibition. AU - Lim,Jong Seung, AU - Park,Yujin, AU - Lee,Byung Mu, AU - Kim,Hyung Sik, AU - Yoon,Sungpil, Y1 - 2016/10/10/ PY - 2016/08/18/received PY - 2016/09/02/accepted PY - 2016/11/1/pubmed PY - 2017/1/28/medline PY - 2016/11/1/entrez KW - COX-2 KW - NS-398 KW - P-gp KW - celecoxib KW - drug-resistant cancer SP - 5063 EP - 5070 JF - Anticancer research JO - Anticancer Res. VL - 36 IS - 10 N2 - BACKGROUND/AIM: Inhibition of cyclooxygenase-2 (COX-2) has been investigated in clinical trials. Currently, NS398 and celecoxib are the most commonly used COX-2 inhibitors. The purpose of this study was to identify conditions that would increase the sensitivity of resistant cancer cells to antimitotic drugs. MATERIALS AND METHODS: We tested whether COX-2 inhibitors can sensitize drug-resistant KBV20C cancer cells. We also compared the efficacy of NS398 with that of celecoxib. RESULTS: Both NS398 and celecoxib could sensitize KB and KBV20C cells to a similar extent, suggesting that COX-2 inhibitors could be used for sensitive, as well as resistant, cancer cells. We demonstrated that the NS398 and celecoxib sensitization mechanism is independent of the inhibition of p-glycoprotein (P-gp), suggesting that resistant KBV20C cells are sensitized through targeting of signaling pathways by both drugs. Furthermore, through using microscopic observation, assessment of cleaved poly ADP ribose polymerase (C-PARP) and annexin V staining we determined that both COX-2 inhibitors strongly sensitized resistant KBV20C cells to vinblastine (VIB) or paclitaxel (PAC) treatment. These results suggest that antimitotic drug-resistant cancer cells can be strongly sensitized by co-treatment with COX-2 inhibitors, without P-gp inhibitory activity. CONCLUSION: These findings provide important information regarding the sensitization of drug-resistant cells and indicate that COX-2 inhibitors may be used for potentially resistant cancer patients, without the toxic effects of P-gp inhibition. SN - 1791-7530 UR - https://www.unboundmedicine.com/medline/citation/27798865/Co_treatment_with_Celecoxib_or_NS398_Strongly_Sensitizes_Resistant_Cancer_Cells_to_Antimitotic_Drugs_Independent_of_P_gp_Inhibition_ L2 - http://ar.iiarjournals.org/cgi/pmidlookup?view=long&pmid=27798865 DB - PRIME DP - Unbound Medicine ER -