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Updated: Sep 14, 2025

Y-90 Radioembolization and PD-1 Inhibitor as Neoadjuvant Treatment in Hepatocellular Carcinoma
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Y-90 Radioembolization and PD-1 Inhibitor as Neoadjuvant Treatment in Hepatocellular Carcinoma

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The effect and related mechanisms of RAC1 GTP on radiotherapy for hepatocellular carcinoma

Xiaoyu Xu1, Zhengxuying Fang1, Wei Jiang1

  • 11Department of Oncology, The Yuyao People's Hospital, Ningbo, China; 2Department of Health Science Center, Medical College of Ningbo University, Ningbo, China; 3Department of Oncology, The Ningbo 7th People's Hospital, Ningbo, China; 4Department of Radiation Oncology, The Affiliated Lihuili Hospital of Ningbo University, Ningbo, China.

Translational Cancer Research
|July 21, 2025
PubMed
Abstract

Insights

Ras-related C3 botulinum toxin substrate 1 (RAC1) is overexpressed in hepatocellular carcinoma (HCC), driving radioresistance. Inhibiting RAC1 GTPase activity may improve HCC radiotherapy outcomes.

Area of Science:

  • Oncology
  • Molecular Biology
  • Radiotherapy Research

Background:

  • Ras-related C3 botulinum toxin substrate 1 (RAC1) is a Rho GTPase involved in cancer progression and treatment resistance.
  • RAC1's role in hepatocellular carcinoma (HCC) radiotherapy has not been thoroughly investigated.
  • Understanding RAC1's function in HCC is crucial for improving radiotherapy efficacy.

Purpose of the Study:

  • To evaluate RAC1 expression and its prognostic value in HCC.
  • To elucidate the mechanisms of radiation-induced RAC1 GTPase activity in radioresistance.
  • To validate RAC1 inhibition as a strategy to enhance HCC radiosensitivity.

Main Methods:

  • Assessed RAC1 expression in HCC tissues using TCGA and immunohistochemistry.
  • Evaluated prognostic significance with Cox regression and nomogram construction.
  • Quantified radiation-induced RAC1 GTP activity and analyzed downstream signaling (p-IκBα/Bcl-xL) and cell cycle dynamics.
  • Utilized NSC23766, a RAC1 inhibitor, to assess pathway-specific effects.

Main Results:

  • RAC1 was significantly overexpressed in HCC, correlating with advanced stages and poor prognosis.
  • Radiation activated RAC1 GTPase in HCC cells, promoting antiapoptotic signaling (p-IκBα/Bcl-xL) and G2/M cell cycle arrest.
  • NSC23766 treatment inhibited radiation-induced IκBα phosphorylation, Bcl-xL upregulation, and cell cycle arrest, thereby reducing radioresistance.

Conclusions:

  • Overexpression of RAC1 in HCC predicts a poor prognosis and contributes to radioresistance via GTP-dependent activation of antiapoptotic pathways and cell cycle modulation.
  • Targeting RAC1 GTPase activity presents a promising therapeutic strategy to enhance HCC radiosensitivity.
Keywords:
Ras-related C3 botulinum toxin substrate 1 (RAC1)hepatocellular carcinoma (HCC)radiation resistance

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