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Ginsenoside Rh2 from ginseng exosomes enhances chemotherapy sensitivity in non-small cell lung cancer by modulating
Jiao Liu1, Menghan Wang2, Maolin Xia2
1Shanghai Key Laboratory of Molecular Imaging, Jiading District Central Hospital Affiliated Shanghai University of Medicine and Health Sciences, Shanghai 201318, China; School of Nursing and Health Management, Shanghai University of Medicine & Health Sciences, Shanghai 201318, China.
Background:
Non-small cell lung cancer (NSCLC) remains a prevalent and malignant cancer globally, characterized by chemotherapy resistance. The aim of this study was focused on the potential of ginsenoside (Gn)-Rh2 from ginseng exosomes (Gn-Exos), a primary bioactive constituent of Panax ginseng, to enhance chemotherapy sensitivity in NSCLC.
Methods:
In this study, Gn-Exo was isolated and identified. The intake and internal organ distribution of PKH26-labelled Gn-Exos was detected using immunofluorescence and in vivo imaging. Transwell migration, 5-ethynyl-2'-deoxyuridine (EdU) incorporation, cell counting, and wound healing experiments were performed to assess NSCLC cell proliferation and migration. A mouse tumor xenograft model was constructed to assess the roles of Gn-Exos and the main active ingredient Gn-Rh2 in NSCLC progression and metastasis in vivo.
Results:
Gn-Exos can inhibit the proliferation, migration, cancer growth, and pulmonary metastasis of NSCLC cells. Mass spectrometry analysis confirmed that the main component of Gn-Exos was Gn-Rh2. The results also showed that Gn-Rh2 inhibited the proliferation and migration of NSCLC cells in both in vivo and in vitro experiments. Comprehensive proteomic analysis identified ribonucleotide reductase regulatory subunit M2 (RRM2) and ubiquitin-specific protease 22 (USP22) as key targets significantly downregulated by Gn-Rh2. Experimental results demonstrated that Gn-Rh2 disrupts the interaction to USP22, disrupting the interaction between USP22 and RRM2, leading to ubiquitination degradation of RRM2. Animal experiments further confirmed that Gn-Rh2 sensitized NSCLC cells to chemotherapy, particularly cisplatin.
Conclusion:
These findings provide novel insights into the molecular mechanisms of Gn-Rh2 in enhancing chemotherapy sensitivity and suggest a promising therapeutic strategy for NSCLC.
Insights
Ginseng exosomes containing ginsenoside Rh2 (Gn-Rh2) inhibit non-small cell lung cancer (NSCLC) progression and metastasis. Gn-Rh2 enhances chemotherapy sensitivity by downregulating RRM2 and USP22, offering a potential NSCLC treatment.
Area of Science:
- Biochemistry
- Molecular Biology
- Oncology
Background:
- Non-small cell lung cancer (NSCLC) is a leading global malignancy with significant chemotherapy resistance.
- Ginseng exosomes (Gn-Exos) contain ginsenoside Rh2 (Gn-Rh2), a bioactive compound from Panax ginseng with potential anti-cancer properties.
Purpose of the Study:
- To investigate the efficacy of Gn-Rh2 from Gn-Exos in overcoming chemotherapy resistance in NSCLC.
- To elucidate the molecular mechanisms underlying Gn-Rh2's effects on NSCLC proliferation, migration, and metastasis.
Main Methods:
- Isolation and identification of Gn-Exos.
- In vivo and in vitro assays to assess NSCLC cell proliferation, migration, and metastasis.
- Mouse tumor xenograft models to evaluate therapeutic effects.
- Mass spectrometry and proteomic analysis to identify molecular targets.
Main Results:
- Gn-Exos and Gn-Rh2 significantly inhibited NSCLC cell proliferation, migration, and metastasis in vitro and in vivo.
- Gn-Rh2 was identified as the primary active component in Gn-Exos.
- Gn-Rh2 downregulated RRM2 and USP22 by disrupting their interaction, leading to RRM2 degradation.
- Gn-Rh2 sensitized NSCLC cells to cisplatin chemotherapy.
Conclusions:
- Gn-Rh2 derived from ginseng exosomes is a potent inhibitor of NSCLC progression and metastasis.
- The molecular mechanism involves the downregulation of RRM2 and USP22, enhancing chemotherapy sensitivity.
- Gn-Rh2 represents a promising therapeutic strategy for NSCLC treatment.
