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Updated: Sep 20, 2025

Gene Regulation and Targeted Therapy in Gastric Cancer Peritoneal Metastasis: Radiological Findings from Dual Energy CT and PET/CT
Published on: January 22, 2018
Inhibition of PDK modulates radiotherapy resistance in gastric cancer
Qi Zhang1, Wanjia Qiao2, Xiaoyu Liu2
1Xi'an International Medical Center Hospital, Xian, 710018, Shanxi, China.
Abstract:
To explore the effect of sodium dichloroacetate (DCA), a pyruvate dehydrogenase kinase (PDK) inhibitor, on the progression of gastric cancer and resistance to radiotherapy, we analyzed histopathological microarrays from 60 gastric cancer and paracancerous tissues to determine PDK expression and its prognostic significance. 5-Ethynyl-2'-deoxyuridine (EdU) incorporation assay and Transwell migration assay were used to investigate the effects of PDK inhibition on gastric cancer cell proliferation and migration. Flow cytometry revealed that PDK inhibition promoted apoptosis and induced G1 phase cell cycle arrest. Colony formation assay combined with radiation was performed to calculate radiobiological parameters, while Western blot detected the expression of phosphorylated histone H2AX (γ-H2AX), a DNA double-strand break marker. Reactive oxygen species (ROS) generation was measured using the fluorescent probe 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA). Our results showed that PDK was highly expressed in gastric cancer tissues and correlated with poor patient prognosis. PDK inhibition suppressed proliferation and migration of gastric cancer cells, promoted apoptosis and G1 phase arrest, and enhanced γ-H2AX accumulation and ROS generation, thereby increasing radiosensitivity. These findings demonstrate that targeting PDK inhibits gastric cancer progression and sensitizes tumor cells to radiotherapy.
Insights
Sodium dichloroacetate (DCA), a pyruvate dehydrogenase kinase (PDK) inhibitor, was found to inhibit gastric cancer progression. Targeting PDK also enhanced tumor cell radiosensitivity by promoting apoptosis and DNA damage.
Area of Science:
- Oncology
- Biochemistry
- Radiotherapy Research
Background:
- Pyruvate dehydrogenase kinase (PDK) is implicated in cancer progression.
- Gastric cancer exhibits resistance to radiotherapy, necessitating novel therapeutic strategies.
Purpose of the Study:
- To investigate the role of PDK in gastric cancer progression and radioresistance.
- To evaluate the therapeutic potential of sodium dichloroacetate (DCA), a PDK inhibitor, in gastric cancer.
Main Methods:
- Analysis of PDK expression in gastric cancer tissues using histopathological microarrays.
- Assessment of DCA's effects on gastric cancer cell proliferation, migration, apoptosis, and cell cycle via EdU incorporation, Transwell assays, and flow cytometry.
- Evaluation of radiosensitizing effects using colony formation assays, Western blot for γ-H2AX, and ROS generation measurements.
Main Results:
- PDK was highly expressed in gastric cancer and associated with poor prognosis.
- PDK inhibition by DCA suppressed cancer cell proliferation and migration.
- PDK inhibition promoted apoptosis, G1 cell cycle arrest, enhanced DNA damage (γ-H2AX), and increased ROS generation, leading to improved radiosensitivity.
Conclusions:
- PDK is a potential therapeutic target for inhibiting gastric cancer progression.
- Targeting PDK with DCA enhances gastric cancer cell radiosensitivity, offering a promising strategy for combined treatment.
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