[LLY-283 inhibits proliferation and metastasis of head and neck squamous cell carcinoma by targeting PRMT5]

Purpose: To explore the effect of LLY-283 on the biological behavior of Head and neck squamous cell carcinoma(HNSCC) proliferation and metastasis through protein arginine methyltransferase 5(PRMT5).

Methods: TCGA database was used to analyze the expression level of PRMT5 in HNSCC tissues and cell lines by RT-PCR and Western blot. Lentiviral technology was used to construct PRMT5 knockdown stable cell line, and analyze the effect of PRMT5 on the biological behavior of HNSCC. Drug killing experiment was used to observe the IC50 changes of LLY-283 in cell lines. Nude mouse xenograft experiments were further tested to observe the biological effects of LLY-283 on HNSCC through PRMT5.

Results: PRMT5 was highly expressed in HNSCC tissues and cell lines, which promoted the proliferation and metastasis of cell lines, and reduced the IC50 value of LLY-283. LLY-283 could significantly reduce the cell proliferation and metastasis, tumor volume and Ki-67 expression in nude mice in vivo of HNSCC through PRMT5.

Conclusions: LLY-283 inhibits the expression of PRMT5 and Ki-67, thereby decreases the proliferation and metastasis of HNSCC and the ability to form transplanted tumors in nude mice, exerting anti-tumor effects.

 

Comments:

The study aimed to investigate the effect of LLY-283, a potential drug, on the biological behavior of Head and Neck Squamous Cell Carcinoma (HNSCC) by targeting Protein Arginine Methyltransferase 5 (PRMT5). The researchers employed various methods to analyze the expression of PRMT5, assess the impact of PRMT5 on HNSCC behavior, determine the IC50 (half maximal inhibitory concentration) of LLY-283 in cell lines, and conduct xenograft experiments using nude mice to observe the effects of LLY-283 on HNSCC in vivo.

The results showed that PRMT5 was highly expressed in both HNSCC tissues and cell lines. This high expression of PRMT5 was associated with increased proliferation and metastasis of the cell lines. Furthermore, it was found that PRMT5 expression reduced the IC50 value of LLY-283, indicating a potential relationship between PRMT5 and drug resistance. Treatment with LLY-283 resulted in a significant reduction in cell proliferation and metastasis. In vivo experiments using nude mice confirmed that LLY-283 decreased tumor volume and the expression of Ki-67, a marker of cell proliferation, in HNSCC through the inhibition of PRMT5.

In conclusion, LLY-283 demonstrated inhibitory effects on the expression of PRMT5 and Ki-67, leading to a decrease in HNSCC proliferation, metastasis, and the ability to form transplanted tumors in nude mice. These findings suggest that LLY-283 may have potential as an anti-tumor therapy for HNSCC by targeting PRMT5.

Related Products

Cat.No.	Product Name	Information
S8883	LLY-283	LLY-283 is a novel and selective inhibitor of protein arginine methyltransferase 5 (PRMT5). LLY-283 inhibits PRMT5 enzymatic activity in vitro and in cells with IC50 of 22 nM and 25 nM, respectively. LLY-283 shows antitumor activity.

Related Targets

PRMT