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Docosahexaenoic Acid Serving As Sensitizing Agents And Gefitinib Resistance Revertants In EGFR Targeting Treatment.
Onco Targets Ther. 2019; 12:10547-10558.OT

Abstract

Objective

Due to the resistance of cancer cells, chemotherapy has been severely restricted. Docosahexaenoic acid (DHA) has been broadly identified as the chemo-sensitizing agent and revertant of multidrug resistance owing to its pleiotropic characteristics; however, it has not been well interpreted. The purpose of this research was to identify the anticancer role of DHA and its combination with the chemotherapeutic agent Gefitinib in non-small cell lung cancer (NSCLC).

Methods

Human chemo-sensitive NSCLC PC-9 cells and the Gefitinib-resistant counterpart PC-9/GR cells were adopted to assess the effects of the integrated DHA and Gefitinib treatments in vitro and vivo, for which the combination index (CI), apoptosis rate and the epithelial growth factor receptor (EGFR) pathway were analyzed.

Results

Comparing with the control cells, the DHA-treated PC-9/GR cells triggered the increase of drug absorption and sensitivity, suggesting that the sensitivity of chemotherapeutic drug could be induced by DHA. Moreover, the elevation of phosphorylation levels of EGFR and the downstream extracellular signal-regulated kinase (ERK) in the cellular lysates were induced by the DHA+Gefitinib treatment. Additionally, the long-term Gefitinib stimulated PC-9 model revealed that DHA could revert the Gefitinib resistance.

Conclusion

This is the first research that indicated the novel biochemical effect of DHA, which can help in overcoming the resistance of EGFR-TKI in NSCLC cells and broaden the horizon of the DHA supplementation during the NSCLC therapy.

Authors+Show Affiliations

Department of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing 211198, People's Republic of China.Department of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing 211198, People's Republic of China.Department of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing 211198, People's Republic of China.Department of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing 211198, People's Republic of China.Department of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing 211198, People's Republic of China.Department of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing 211198, People's Republic of China.Department of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing 211198, People's Republic of China.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31819534

Citation

Ding, Xuansheng, et al. "Docosahexaenoic Acid Serving as Sensitizing Agents and Gefitinib Resistance Revertants in EGFR Targeting Treatment." OncoTargets and Therapy, vol. 12, 2019, pp. 10547-10558.
Ding X, Ge L, Yan A, et al. Docosahexaenoic Acid Serving As Sensitizing Agents And Gefitinib Resistance Revertants In EGFR Targeting Treatment. Onco Targets Ther. 2019;12:10547-10558.
Ding, X., Ge, L., Yan, A., Ding, Y., Tao, J., Liu, Q., & Qiao, C. (2019). Docosahexaenoic Acid Serving As Sensitizing Agents And Gefitinib Resistance Revertants In EGFR Targeting Treatment. OncoTargets and Therapy, 12, 10547-10558. https://doi.org/10.2147/OTT.S225918
Ding X, et al. Docosahexaenoic Acid Serving as Sensitizing Agents and Gefitinib Resistance Revertants in EGFR Targeting Treatment. Onco Targets Ther. 2019;12:10547-10558. PubMed PMID: 31819534.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Docosahexaenoic Acid Serving As Sensitizing Agents And Gefitinib Resistance Revertants In EGFR Targeting Treatment. AU - Ding,Xuansheng, AU - Ge,Lei, AU - Yan,Aiwen, AU - Ding,Yuyin, AU - Tao,Junye, AU - Liu,Qianqian, AU - Qiao,Chen, Y1 - 2019/12/02/ PY - 2019/08/03/received PY - 2019/10/31/accepted PY - 2019/12/11/entrez PY - 2019/12/11/pubmed PY - 2019/12/11/medline KW - DHA KW - drug resistance KW - non-small cell lung cancer SP - 10547 EP - 10558 JF - OncoTargets and therapy JO - Onco Targets Ther VL - 12 N2 - Objective: Due to the resistance of cancer cells, chemotherapy has been severely restricted. Docosahexaenoic acid (DHA) has been broadly identified as the chemo-sensitizing agent and revertant of multidrug resistance owing to its pleiotropic characteristics; however, it has not been well interpreted. The purpose of this research was to identify the anticancer role of DHA and its combination with the chemotherapeutic agent Gefitinib in non-small cell lung cancer (NSCLC). Methods: Human chemo-sensitive NSCLC PC-9 cells and the Gefitinib-resistant counterpart PC-9/GR cells were adopted to assess the effects of the integrated DHA and Gefitinib treatments in vitro and vivo, for which the combination index (CI), apoptosis rate and the epithelial growth factor receptor (EGFR) pathway were analyzed. Results: Comparing with the control cells, the DHA-treated PC-9/GR cells triggered the increase of drug absorption and sensitivity, suggesting that the sensitivity of chemotherapeutic drug could be induced by DHA. Moreover, the elevation of phosphorylation levels of EGFR and the downstream extracellular signal-regulated kinase (ERK) in the cellular lysates were induced by the DHA+Gefitinib treatment. Additionally, the long-term Gefitinib stimulated PC-9 model revealed that DHA could revert the Gefitinib resistance. Conclusion: This is the first research that indicated the novel biochemical effect of DHA, which can help in overcoming the resistance of EGFR-TKI in NSCLC cells and broaden the horizon of the DHA supplementation during the NSCLC therapy. SN - 1178-6930 UR - https://www.unboundmedicine.com/medline/citation/31819534/Docosahexaenoic_Acid_Serving_As_Sensitizing_Agents_And_Gefitinib_Resistance_Revertants_In_EGFR_Targeting_Treatment L2 - https://dx.doi.org/10.2147/OTT.S225918 DB - PRIME DP - Unbound Medicine ER -
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