Targeting Cancer Metabolism to Resensitize Chemotherapy: Potential Development of Cancer Chemosensitizers from Traditional Chinese Medicines

Guo, Wei; Tan, Hor‐Yue; Chen, Feiyu; Wang, Ning; Feng, Yibin

doi:10.3390/cancers12020404

“…To support the rapid proliferation, progression, and metastasis, cancer cells rewire metabolic pathways via increased generation of adenosine triphosphate (ATP), macromolecule synthesis, and antioxidant regeneration ( 39 ). Abnormal metabolic pathways provide new targets for the treatment of cancer and sensitize cancer chemotherapy ( 40 ). For example, increased expression of MUC1 enhanced glycolysis, nonoxidative PPP, and pyrimidine biosynthesis ( 41 ).…”

Section: Discussionmentioning

confidence: 99%

A Combined Epithelial Mesenchymal Transformation and DNA Repair Gene Panel in Colorectal Cancer With Prognostic and Therapeutic Implication

Huang

¹

,

Liu

²

,

Liu

³

et al. 2021

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BackgroundEpithelial mesenchymal transformation (EMT) and DNA repair status represent intrinsic features of colorectal cancer (CRC) and are associated with patient prognosis and treatment responsiveness. We sought to develop a combined EMT and DNA repair gene panel with potential application in patient classification and precise treatment.MethodsWe comprehensively evaluated the EMT and DNA repair patterns of 1,652 CRC patients from four datasets. Unsupervised clustering was used for classification. The clinical features, genetic mutation, tumor mutation load, and chemotherapy as well as immunotherapy sensitivity among different clusters were systematically compared. The least absolute shrinkage and selection operator regression method was used to develop the risk model.ResultsThree distinct CRC clusters were determined. Clustet1 was characterized by down-regulated DNA repair pathways but active epithelial markers and metabolism pathway and had intermediate prognosis. Clustet2 was characterized by down-regulated both epithelial markers and DNA repair pathways and had poor outcome. Clustet3 presented with activation of DNA repair pathway and epithelial markers had favorable prognosis. Clustet1 might benefit form chemotherapy and Clustet3 had a higher response rate to immunotherapy. An EMT and DNA repair risk model related to prognosis and treatment response was developed.ConclusionsThis work developed and validated a combined EMT and DNA repair gene panel for CRC classification, which may be an effective tool for survival prediction and treatment guidance in CRC patients.

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“…The ancillary efficacy of Chinese medicines for tumour treatment is definite, in addition to the limited side-effects. Although Chinese medicines are limited in their ability to shrink tumours, they help to improve patient symptoms, stabilise tumours, and improve patient quality of life, leading to long-term, high-quality survival with tumours [ 39 , 40 ].…”

Section: Discussionmentioning

confidence: 99%

Combined Treatment of Non‐Small‐Cell Lung Cancer Using Shenyi Capsule and Platinum‐Based Chemotherapy: A Meta‐Analysis and Systematic Review

Xu

¹

,

Peng

²

,

Han

³

et al. 2020

Evidence-Based Complementary and Alternative Medicine

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Background.The efficacy and safety of combined treatment of non-small-cell lung cancer (NSCLC) using Shenyi capsules and platinum-based chemotherapy were comprehensively evaluated. Methods. A computer-based search was used to identify reports on clinical randomized controlled trials (RCTs) on this combined treatment for NSCLC from the PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), VIP, China Biomedical (CBM), and Wanfang Data electronic databases. The databases were searched from their start to February 2020. The quality of the included studies was evaluated and then crosschecked by two independent evaluators. A meta-analysis was conducted using RevMan5.3. Results. A total of 27 RCTs involving 2,663 patients were included in the meta-analysis, including 1,380 and 1,283 patients in the treatment and control groups, respectively. The results of the meta-analysis showed that, compared to platinum-based chemotherapy alone, the 1-year survival rate (relative risk (RR) = 1.27, 95% confidence interval (CI) [1.10, 1.47], P < 0.01 ), 2-year survival rate (RR = 1.35, 95% CI [1.10, 1.65], P < 0.01 ), objective tumour remission rate (RR = 1.52, 95% CI [1.35, 1.71], P < 0.01 ), and body CD4+/CD8+ ratio (standardized mean difference (SMD) = 0.12, 95% CI [0.07, 0.17], P < 0.01 ) were increased for the combined treatment of NSCLC using Shenyi capsules and platinum-based chemotherapy; moreover, quality of life was also improved (RR = 2.09, 95%CI [1.75, 2.50], P < 0.01 ) and it reduced leukocyte toxicity (RR = 0.49, 95%CI [0.39, 0.63], P < 0.01 ), haemoglobin toxicity (RR = 0.48, 95% CI [0.28, 0.81], P < 0.01 ), platelet toxicity (RR = 0.44, 95% CI [0.28, 0.70], P < 0.01 ), vomiting reaction (RR = 0.60, 95% CI [0.45, 0.78], P < 0.01 ), and serum vascular endothelial growth factor level (SMD = −63.67, 95% CI [−67.59, −59.75], P < 0.01 ). Conclusions. The treatment of NSCLC using Shenyi capsules together with routine platinum-based chemotherapy could enhance short- and long-term efficacy, improve patient quality of life, alleviate toxicity and side-effects of platinum-based chemotherapeutic drugs, boost body immune function, and inhibit tumour neovascularisation. These findings require further validation in large-sample, high-quality RCTs.

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“…TCM holds the unique advantages of multi-target and multi-pathway regulation in the treatment of complex diseases with high e cacy, low toxicity, and few side effects [4][5][6][7][8][9] . Previous research illustrated that RJSJ is safe and well tolerated, and it does not induce body weight loss, immune dysregulation, or myelosuppression in mice 13 .…”

Section: Discussionmentioning

confidence: 99%

“…The characteristics and advantages of traditional Chinese medicine (TCM) in the prevention and treatment of complex diseases, such as cancers, cardiovascular diseases, infectious diseases, metabolic diseases, and neurodegenerative diseases, have attracted global attention, and such treatments have been illustrated to ameliorate symptoms, improve patient quality of life, and prolong survival [4][5][6][7][8][9] . In 2018, the WHO International Classi cation of Diseases listed traditional medicines, including TCM, in its classi cation system for the rst time 10 .…”

Section: Introductionmentioning

confidence: 99%

Ruanjian Sanjie Decoction Induces Apoptosis in Triple-negative Breast Cancer Cells by Downregulating cIAP1/2 and XIAP

Zhao¹,

Wang²,

Jia³

et al. 2020

Preprint

0

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Background: Traditional Chinese medicine (TCM) comprises a unique theoretical system developed over thousands of years. The previous study reported that Ruanjian Sanjie (RJSJ) exerts anti-tumor effects by inducing cell apoptosis. However, the mechanism is not clear. Methods: In this study, we investigated the possible mechanism by the strategy of combining network pharmacology analysis with experiment (in vitro and in vivo). First, four kinds of breast cancer cell lines were used to conduct proliferation, apoptosis and cell cycle analysis. Secondly, to study pathophysiological processes of breast cancer at the molecular network level, we for the first time constructed an “integrated apoptosis module network of breast cancer” by assembling the regulatory relationships of canonical apoptosis signaling pathways. Through the strategy of combining network analysis and experiments, we analyzed the main mechanism of RJSJ in breast cancer and screened out the core genes. We further studied the inhibitory effect of RJSJ combined with carboplatin (CBP) in vivo. Finally, the synergistic effect of RJSJ and CBP were analyzed and the potential active components in RJSJ were predicted.Results: This study demonstrated that RJSJ could significantly inhibit breast cancer cell proliferation and induce apoptosis in a concentration-dependent manner. The primary mechanism of RJSJ in the treatment of breast cancer was pro-apoptotic. The core apoptosis genes regulated by RJSJ were cIAP1/2 and XIAP. We also found that RJSJ in combination with CBP tended to synergistically induce apoptosis, which might mainly be achieved through the regulation of multiple targets and pathways. Alexandrin (BX05, XKC02, SCG01), baicalin (BX22), guanosine (BX32), arjunglucoside I (XKC10) etc. were predicted as potential active components.Conclusions: These findings provide the rationale for exploring the therapeutic effects of RJSJ against breast cancer and providing a bridge for the combined use of Chinese and Western medicine.

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Targeting Cancer Metabolism to Resensitize Chemotherapy: Potential Development of Cancer Chemosensitizers from Traditional Chinese Medicines

Cited by 47 publications

References 127 publications

A Combined Epithelial Mesenchymal Transformation and DNA Repair Gene Panel in Colorectal Cancer With Prognostic and Therapeutic Implication

A Combined Epithelial Mesenchymal Transformation and DNA Repair Gene Panel in Colorectal Cancer With Prognostic and Therapeutic Implication

Combined Treatment of Non‐Small‐Cell Lung Cancer Using Shenyi Capsule and Platinum‐Based Chemotherapy: A Meta‐Analysis and Systematic Review

Ruanjian Sanjie Decoction Induces Apoptosis in Triple-negative Breast Cancer Cells by Downregulating cIAP1/2 and XIAP

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