MG132 reverse the malignant characteristics of hypopharyngeal cancer
Juke Ma1, Liang Yu1, Jiajun Tian1
1Department of Otolaryngology-Head and Neck Surgery, Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China.
Abstract:
In order to reverse the malignant characteristics of hypopharyngeal cancer, the proteasome inhibitor MG132 was introduced into FaDu/T cells and the mechanisms underlying its effects were investigated. The multi-drug resistance (MDR) sensitivities of FaDu/T and FaDu/T-MG132 cancer cells to several chemotherapeutics were investigated by a 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyltetrazolium bromide (MTT) assay. Apoptosis was measured by staining cells with Annexin V and propidium iodide (PI) double staining. Reverse transcription-polymerase chain reaction and western blot analysis were conducted to detect mRNA and corresponding protein levels of the MDR- and apoptosis-related genes P-glycoprotein (P-gp), caspase-3, Bcl-2 and Bax. The nuclear protein of nuclear factor κ-light-chain-enhancer of activated B cells. (NF-κB) and p53 were also investigated via western blot analysis. Compared with FaDu/T cells, the drug resistance of FaDu/T + MG132 cells to cisplatin (DDP), 5-fluorouracil (5-FU), doxorubicin (Dox) and vincristine (VCR) decreased. With increased expression of caspase-3 and Bax and decreased expression of Bcl-2, the anti-apoptotic ability markedly decreased in FaDu/T + MG132 cells. P-gp and NF-κB significantly decreased; however, p53 increased in FaDu/T + MG132 cells. These results suggested that the proteasome inhibitor MG132 reversed the malignant characteristics of FaDu/T by enhancing apoptosis and inhibiting P-gp. MG132 was also able to inhibit the nuclear translocation of NF-κB and increase the expression of p53.
Insights
The proteasome inhibitor MG132 reverses hypopharyngeal cancer cell malignancy by enhancing apoptosis and reducing drug resistance. It inhibits P-glycoprotein and nuclear factor-kappa B, while increasing p53 expression.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Hypopharyngeal cancer exhibits malignant characteristics, including multi-drug resistance (MDR).
- Proteasome inhibitors offer potential therapeutic strategies for reversing cancer cell malignancy.
Purpose of the Study:
- To investigate the effects of the proteasome inhibitor MG132 on FaDu/T hypopharyngeal cancer cells.
- To elucidate the mechanisms by which MG132 reverses malignant characteristics, focusing on MDR and apoptosis.
Main Methods:
- Multi-drug resistance (MDR) was assessed using a 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyltetrazolium bromide (MTT) assay.
- Apoptosis was evaluated via Annexin V and propidium iodide (PI) double staining.
- Gene and protein expression levels of P-glycoprotein (P-gp), caspase-3, Bcl-2, Bax, nuclear factor-kappa B (NF-κB), and p53 were analyzed using RT-PCR and Western blot.
Main Results:
- MG132 treatment decreased the drug resistance of FaDu/T cells to cisplatin, 5-fluorouracil, doxorubicin, and vincristine.
- MG132 enhanced apoptosis by increasing caspase-3 and Bax expression while decreasing Bcl-2 expression.
- MG132 significantly reduced P-glycoprotein (P-gp) and nuclear factor-kappa B (NF-κB) levels, and increased p53 expression.
Conclusions:
- The proteasome inhibitor MG132 effectively reverses malignant characteristics in hypopharyngeal cancer cells.
- MG132 exerts its effects by enhancing apoptosis, inhibiting P-gp, reducing NF-κB nuclear translocation, and increasing p53 expression.
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