2. Academic Validation
  3. Y-27632 Suppresses the Growth and Migration of Oral Squamous Cell Carcinoma, but Upregulates Autophagy by Suppressing mTOR Effectors

Y-27632 Suppresses the Growth and Migration of Oral Squamous Cell Carcinoma, but Upregulates Autophagy by Suppressing mTOR Effectors

  • J Oral Pathol Med. 2025 Apr;54(4):207-216. doi: 10.1111/jop.13603.
Jie Wen 1 2,  Yunhan Sun 1 2,  Li Ma 1,  Tingjian Zu 1 2,  Na Wang 3,  Tianqi Zhang 1,  Jin Liang 1 2,  Yulei Zhang 2,  Haoyang Lu 1,  Yihua Wu 4,  Shizhou Zhang 1
Affiliations

Affiliations

  • 1 Department of Oral and Maxillofacial Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China.
  • 2 School of Stomatology, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, China.
  • 3 Department of Stomatology, Affiliated Hospital of Heze Medical College, Heze, Shandong, China.
  • 4 Department of Periodontology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China.
PMID: 39921531 DOI: 10.1111/jop.13603
Abstract

Background: The Rho-associated protein kinase (ROCK) inhibitor Y-27632 is a potential immunotherapeutic agent for Cancer treatment. Y-27632 blocks the growth and migration of oral squamous cell carcinoma (OSCC) CAL-27 cells. However, detailed studies on the underlying mechanisms have not yet been reported.

Methods: We investigated the effects of Y-27632 on the proliferation, migration, and invasion of OSCC cells (CAL-27, SCC-4, and SCC-9) using the Cell Counting Kit-8 assay, ethynyl-2'-deoxyuridine staining, cell scratch, and transwell assay in vitro. Next, ROCK1/2 was knocked down using siRNA to confirm that the effects of Y-27632 were mediated by the inhibition of ROCK activity. A xenograft mouse model was used to verify the effects of Y-27632 in vivo. The mechanisms underlying Y-27632-induced tumor suppression were detected using western blotting and qRT-PCR.

Results: Our data demonstrated that Y-27632 potently inhibited OSCC cells (CAL-27, SCC-4, and SCC-9) by inhibiting ROCK activity. In vivo assays confirmed that Y-27632 suppressed OSCC growth by reducing cell proliferation. Biochemical assays demonstrated that Y-27632 inactivated the Akt pathway, and treatment with SC79, an Akt Activator, rescued the cell growth and migration inhibition elicited by Y-27632. Further investigation revealed that Y-27632 enhanced Autophagy by suppressing the Akt/mTOR pathway.

Conclusion: Our study demonstrated that Y-27632 significantly suppressed the growth and migration of OSCC cells and upregulated Autophagy via the Akt/mTOR pathway, thus providing a potential therapeutic drug for patients with OSCC.

Keywords

AKT/mTOR; Rho‐associated protein kinase; Y‐27632; autophagy; oral squamous cell carcinoma.

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