Efficacy and Safety of Compound Kushen Injection on Patients with Advanced Colon Cancer: A Meta‐Analysis of Randomized Controlled Trials

Yu, Lixiu; Zhou, Ying; Yu, Yang; Lu, Fanghong; Fan, Yeqin

doi:10.1155/2017/7102514

Cited by 37 publications

(41 citation statements)

References 31 publications

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“…dIsCussIon CKI, as a TCM formula, has been approved by NMPA to treat cancer-induced pain. 17 The application of CKI for the treatment of a variety of cancer types has also been studied in breast cancer, 19 colon cancer, 20 nonsmall cell lung cancer, 21 acute leukemia, 22 and HCC. [23][24][25] Sorafenib, the first frontline drug, has been widely used for advanced HCC therapy for a long time.…”

Section: Cki Sensitizes Hcc To the Therapeutic Effects Of Subclinicalmentioning

confidence: 99%

“…[17][18][19] CKI has been applied to treat various solid tumor types clinically for the last 20 years, including liver cancer, lung cancer, breast cancer, gastric cancer, colorectal cancer, and other cancer types. [18][19][20][21][22] Notably, CKI was found to be effective in treating cancer-induced pain via the transient receptor potential cation channel subfamily V member 1 signaling. 17 Previous reports have shown that CKI used alone or combined with conventional chemotherapy enhances antitumor efficacy, reduces chemotherapy-induced toxicity, and improves quality of life.…”

Section: Introductionmentioning

confidence: 99%

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Compound kushen injection relieves tumor-associated macrophage-mediated immunosuppression through TNFR1 and sensitizes hepatocellular carcinoma to sorafenib

Yang

Sun

Yao

et al. 2020

J Immunother Cancer

107

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BackgroundThere is an urgent need for effective treatments for hepatocellular carcinoma (HCC). Immunotherapy is promising especially when combined with traditional therapies. This study aimed to investigate the immunomodulatory function of an approved Chinese medicine formula, compound kushen injection (CKI), and its anti-HCC efficiency in combination with low-dose sorafenib.MethodsGrowth of two murine HCC cells was evaluated in an orthotopic model, a subcutaneous model, two postsurgical recurrence model, and a tumor rechallenge model with CKI and low-dose sorafenib combination treatment. In vivo macrophage or CD8+T cell depletion and in vitro primary cell coculture models were used to determine the regulation of CKI on macrophages and CD8+T cells.ResultsCKI significantly enhanced the anticancer activity of sorafenib at a subclinical dose with no obvious side effects. CKI and sorafenib combination treatment prevented the postsurgical recurrence and rechallenged tumor growth. Further, we showed that CKI activated proinflammatory responses and relieved immunosuppression of tumor-associated macrophages in the HCC microenvironment by triggering tumor necrosis factor receptor superfamily member 1 (TNFR1)-mediated NF-κB and p38 MAPK signaling cascades. CKI-primed macrophages significantly promoted the proliferation and the cytotoxic ability of CD8+T cells and decreased the exhaustion, which subsequently resulted in apoptosis of HCC cells.ConclusionsCKI acts on macrophages and CD8+T cells to reshape the immune microenvironment of HCC, which improves the therapeutic outcomes of low-dose sorafenib and avoids adverse chemotherapy effects. Our study shows that traditional Chinese medicines with immunomodulatory properties can potentiate chemotherapeutic drugs and provide a promising approach for HCC treatment.

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Section: Cki Sensitizes Hcc To the Therapeutic Effects Of Subclinicalmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Compound kushen injection relieves tumor-associated macrophage-mediated immunosuppression through TNFR1 and sensitizes hepatocellular carcinoma to sorafenib

Yang

Sun

Yao

et al. 2020

J Immunother Cancer

107

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“…CKI is an ancient formulation in the Chinese pharmacopoeia; derived from a mixture of Radix sophorae flavescentis and Rhizoma smilactis glabrae herbs. Mixed results have been reported in breast cancer 51 . Here, we found CKI to down-regulate P53 pathway which is in line with a previous observation of P53 independent apoptotic cell death 17 , and up-regulate RTK-RAS-MAPK (EGFR, p38 and ErbB), PI3K-Akt-mTOR, NRF2 and TGF-beta pathways in MCF-7.…”

Section: Discussionmentioning

confidence: 92%

A systems pharmacology approach to determine the mechanisms of action of pleiotropic natural products in breast cancer from transcriptome data

Odongo

Zergeroǧlu

Çakır

2020

Preprint

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7 Background 8 Plant-derived natural products possess poly-pharmacologic 9 mechanisms of action with good tolerability and thus are Results 1 The signalling pathways regulated by the pleiotropic effects of 2 Actein, Withaferin A, Indole-3-Carbinol and Compound 3 Kushen were found to be projected on a set of oncogenesis 4 processes at the transcriptomic level in different breast cancer 5 subtypes (triple negative, luminal A and HER2+). Notably, 6 these compounds indirectly regulated known oncogenes in the 7 different subtypes through their associated pathways in the 8 subnetworks.9

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“…Compound Kushen Injection (CKI) is a traditional Chinese medicinal preparation that is widely used in clinics. Several recent meta-analyses were the most comprehensive analyses undertaken of currently available data regarding the treatment of patients with colon cancer and other advanced cancers with CKI combined with radiotherapy [6,14,15]. In these clinical reports, CKI enhanced the efficacy and reduced the toxic side effects of chemotherapeutic drugs since CKI improves immune function in patients with advanced cancer, thereby enhancing therapeutic efficacy [16].…”

Section: Discussionmentioning

confidence: 99%

“…CKI has been extensively used to treat cancer patients in a Chinese clinical setting in combination with chemotherapy for more than 15 years. Randomized controlled trials show significant efficacy of CKI in the treatment of advanced cancer especially colorectal cancer [6]. It has been demonstrated that CKI decreased the growth of colorectal cancer [7], hepatic carcinoma [8], human breast cancer [9], and gastric cancer cells [10]in vitro.…”

Section: Introductionmentioning

confidence: 99%

Cell Cycle Arrest and Autophagy Induced by Compound Kushen Injection in sw620 and sw480 Colorectal Cancer Cells with p53 Mutation

Sun

Wang

et al. 2019

Preprint

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Background Compound Kushen Injection (CKI) has been clinically used in China for 15 years to treat various types of solid tumors, including colorectal cancer. Here we examine cell cycle arrest, induced autophagy, and mutant p53 pathways perturbed by CKI in colorectal cancer cells. We and other groups have shown that CKI alters p53 gene expression patterns and suppresses proliferation in colorectal cancer cells. Methods We measured the effect of CKI on cell proliferation, cell cycle progression and autophagy in sw480 and sw620 colorectal cancer cells in vitro, and carcinogenesis and the progression of azoxymethane/dextran sodium sulfate-induced colorectal cancer in ICR mice in vivo. We also used RNA sequencing to analyze mRNA expression altered by CKI, and further validated the expression of mutant p53 and several genes in the cell cycle pathway using reverse transcriptase-quantitative PCR and western blotting. Using network pharmacology (BATMAN-TCM database), we have also predicted the active ingredients in CKI involved in regulating the expression of mutant p53. Results We show evidence that CKI significantly suppressed proliferation and cell cycle progression, and induced autophagy of sw480 and sw620 cells in vitro; it also inhibited the development of inflammatory colorectal cancer in vivo. We also show that the down-regulated expression of mutant p53 and adjustments in several key genes related closely to cell-cycle progression. Furthermore, N-oxysophocarpine, lupenone, and geranylacetone were predicted to be the active ingredients of CKI involved in the down-regulated expression of mutant p53. Conclusion Our results indicate that CKI likely acts as a potential anti-cancer therapeutic agent that targets the cell cycle pathway, suggesting a key role in the development of a novel subsidiary therapeutic approach against mutant p53 in patients with colorectal cancer.

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Efficacy and Safety of Compound Kushen Injection on Patients with Advanced Colon Cancer: A Meta‐Analysis of Randomized Controlled Trials

Cited by 37 publications

References 31 publications

Compound kushen injection relieves tumor-associated macrophage-mediated immunosuppression through TNFR1 and sensitizes hepatocellular carcinoma to sorafenib

Compound kushen injection relieves tumor-associated macrophage-mediated immunosuppression through TNFR1 and sensitizes hepatocellular carcinoma to sorafenib

A systems pharmacology approach to determine the mechanisms of action of pleiotropic natural products in breast cancer from transcriptome data

Cell Cycle Arrest and Autophagy Induced by Compound Kushen Injection in sw620 and sw480 Colorectal Cancer Cells with p53 Mutation

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