Curcumin Increases Radiosensitivity of Radioresistant Nasopharyngeal Cancer

Discov Med. 2023 Jun;35(176):418-428. doi: 10.24976/Discov.Med.202335176.42.

Abstract

Objectives: To study the effects of curcumin on the proliferation, invasion, apoptosis, and radiosensitivity of the radioresistant nasopharyngeal carcinoma (NPC) C6661-IR strain as well as the potential radiosensitization mechanism.

Methods: NPC cells were continuously irradiated with different intensities of radiation to induce radiation-resistant cell lines. A plate clone formation assay was used to evaluate the effect of curcumin on the radiosensitivity of NPC cells. 3-(4,5-Dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide thiazolyl blue (MTT) assay was conducted to detect changes in cell viability. Flow cytometry was employed to analyze apoptosis percentage as well as Transwell® assay and immunofluorescence assay to observe cell invasion. Western blotting was applied to detect the expression levels of Bax, Bcl-2, and pro/cleaved-caspase 3. MiR-205-5p mimics and si-TP53INP1 were synthesized and transfected into C6661-IR cells, and the cells were then incubated with 10 μm/L curcumin. Real-time quantitative reverse transcription PCR (RT-qPCR) was used to measure miR-205-5p levels and western blotting was conducted to detect the expression of TP53INP1.

Results: The optimal radiation dose of X-ray was 6 Gy, and this dose was used in all subsequent experiments. Curcumin treatment significantly inhibited the proliferation and invasion of C6661-IR cells, promoted apoptosis and enhanced radiosensitivity. Compared to the 0 Gy+Cur group and the 6 Gy+Cur group, the miR-205-5p levels were higher in the C6661-IR cells of the 0 Gy and 6 Gy groups. Moreover, miR-204-5p was found to directly target TP53INP1. Curcumin downregulated miR-205-5p levels and upregulated TP53INP1 expression (p < 0.05). Thus, modulation of miR-205-5p or TP53INP1 expression attenuates the biological effects of curcumin on C6661-IR cells.

Conclusions: Curcumin inhibited the proliferation and invasion of C6661-IR, promoted apoptosis, and enhanced its radiosensitivity to X-rays by mediating miR-205-5p/TP53INP1 expression.

Keywords: TP53INP1; curcumin; miR-205-5p; radioresistant NPC strain; radiosensitization.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis
  • Carrier Proteins / metabolism
  • Cell Line, Tumor
  • Cell Proliferation
  • Curcumin* / pharmacology
  • Curcumin* / therapeutic use
  • Gene Expression Regulation, Neoplastic
  • Heat-Shock Proteins / metabolism
  • Humans
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Nasopharyngeal Carcinoma / drug therapy
  • Nasopharyngeal Carcinoma / radiotherapy
  • Nasopharyngeal Neoplasms* / drug therapy
  • Nasopharyngeal Neoplasms* / genetics
  • Nasopharyngeal Neoplasms* / radiotherapy
  • Radiation Tolerance

Substances

  • Curcumin
  • MicroRNAs
  • TP53INP1 protein, human
  • Carrier Proteins
  • Heat-Shock Proteins
  • MIRN204 microRNA, human