Adjunctive effect of compound Kushen injection for cancer: An overview of systematic reviews

Li, Chenchen; Dong, Ning; Zhu, Ranpei; Yan, Xiaoyu; Qu, Haoran; Zhang, Yaling; Zheng, Yuling

doi:10.1016/j.jep.2023.116778

Cited by 14 publications

(2 citation statements)

References 25 publications

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“…However, due to the current low quality of research methodology and evidence, its effectiveness needs to be confirmed by more high-quality evidence-based medical evidence. 45 In this systematic review and meta-analysis, we incorporated evidence from the most recent studies and had some strengths over previous reviews. (1) We performed several predefined subgroup analyzes for ORR and DCR according to the retrieved data, finding that both 15 and 20 ml/day of CKI combined with FOLFOX were effective in ORR.…”

Section: Discussionmentioning

confidence: 99%

Efficacy and Safety of Compound Kushen Injection for Advanced Colorectal Cancer: A Systematic Review and Meta-Analysis of Randomized Clinical Trials with Trial Sequential Analysis

Wu,

Ma,

Wang

et al. 2024

Integr Cancer Ther

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Backgrounds: Colorectal cancer (CRC) is one of the common malignant tumors, with a gradually increasing incidence. Due to late detection and poor sensitivity to chemotherapy, it has become a difficult problem in tumor prevention and treatment at present. Exploring or discovering new combinations is a significant strategy for the treatment of CRC. Compound kushen injection (CKI) is a traditional Chinese medicine injection extracted from Sophora flavescens Ait. and Smilax glabra Roxb., which is widely used in the comprehensive treatment of CRC in China. This systematic review is aimed to ascertain the clinical efficacy and safety of CKI combined with chemotherapy in the treatment of advanced CRC based on available data. On this basis, the specific application of CKI in combination with chemotherapy in clinical practice is further discussed. Methods: PubMed, Web of Science, the Cochrane Library, EMBASE, China National Knowledge Infrastructure, Chinese Scientific Journals Database, Wanfang Database, Chinese Biomedicine Database Searches, the Chinese Clinical Trial Registry, and ClinicalTrials.gov were searched systematically, from inception to April 20, 2024. We adopted the ROB2 tool to assess quality of the included trials, Stata 16 for data analysis, and evaluated the publication bias with the funnel plot and Egger’s test. The quality of the evidence was justified according to GRADE. We also used trial sequential analysis (TSA) to calculate the final required sample size in this meta-analysis and to verify whether the results present a reliable conclusion. The protocol for this systematic review was registered on PROSPERO (CRD42022380106) and has been published. Results: Sixteen trials that examined 1378 patients were included in this study. Meta-analysis revealed that compared with chemotherapy, objective response rate (ORR, RR = 1.30, 95% CI: 1.18-1.44), disease control rate (DCR, RR = 1.08, 95% CI: 1.03-1.13), and KPS score improvement rate were improved (RR = 1.18, 95% CI: 1.07-1.31) by the combination of CKI and chemotherapy in patients with advanced CRC. Additionally, CKI combined with chemotherapy was associated with lower adverse reactions such as leukopenia (RR = 0.74, 95% CI: 0.62-0.87), thrombocytopenia (RR = 0.68, 95% CI: 0.49-0.94), gastrointestinal reactions (RR = 0.72, 95% CI: 0.55-0.94), and liver damage (RR = 0.48, 95% CI: 0.30-0.79), higher CD4+ ratio (MD = 9.70, 95% CI:8.73-10.68) and CD4+/CD8+ ratio (MD = 0.25, 95% CI: 0.22-0.28), and lower CD8+ T cell ratio (MD = −5.25, 95% CI: −5.94 to −4.56). Subgroup analysis demonstrated that ORR and DCR in patients with advanced CRC were improved when CKI combined with FOLFOX and 5Fu + L-OHP. Both 15 and 20 ml/day of CKI combined with FOLFOX provided a significant effect in ORR. Moreover, ORR was improved when the accumulated CKI dose reached 280 ml per course and 420 ml in total. 7 days/course as well as 14 days/course of CKI combined with FOLFOX were effective durations in ORR. As for DCR, 7 days/course of CKI combined with FOLFOX could improve efficacy. Furthermore, CKI + FOLFOX may be useful in ORR and DCR for at least 4 cycles of combination therapies. The TSA showed that firm results in ORR and DCR were established and additional trials were unlikely to change the results. Conclusion: CKI combined with chemotherapy provides a statistically significant and clinically important effect in the improvement of ORR, DCR, performance status, ADR reduction, and immune function in patients with CRC. However, more rigorously designed, large-scale, and multi-center RCTs are needed in the future.

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Section: Discussionmentioning

confidence: 99%

Efficacy and Safety of Compound Kushen Injection for Advanced Colorectal Cancer: A Systematic Review and Meta-Analysis of Randomized Clinical Trials with Trial Sequential Analysis

Wu,

Ma,

Wang

et al. 2024

Integr Cancer Ther

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“…In the treatment of breast cancer, the herbal prescription has gradually occupied an important position, due to its high security and fewer side effects (Kim et al, 2015;Lopes et al, 2017). For example, the Kushen injection has been demonstrated to show a significant anti-tumor effect in non-small cell lung cancer, gastric cancer, breast cancer, and colorectal cancer (Li, Niu, et al, 2023). Berberine was reported to suppress breast cancer cell growth and metastasis under a hypoxic microenvironment, which provides a candidate herb for breast cancer treatment (Sun et al, 2023).…”

Section: Introductionmentioning

confidence: 99%

Pharmacokinetic study of the interaction between luteolin and magnoflorine in rats

Liu,

2023

Chem Biol Drug Des

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Both luteolin and magnoflorine have been reported to regulate the development of breast cancer, which makes them easier to co‐administrate. Luteolin was co‐administrated with magnoflorine to evaluate their potential interaction. The pharmacokinetic study was performed on male Sprague–Dawley rats randomly grouped as the single administration of luteolin and the co‐administration of luteolin and magnoflorine with six rats of each. CaCO‐2 cell transwell assay was employed for transport evaluation, and the metabolic stability of luteolin and CYP3A activity were assessed in rat liver microsomes. The effect of luteolin on MDA‐MB‐231 cells was assessed with CCK8 assay. Magnoflorine significantly changed the pharmacokinetic profile of luteolin with increased area under the curve (AUC), prolonged t1/2, and reduced clearance rate. Magnoflorine also suppressed the efflux ratio and improved the in vitro metabolic stability of luteolin. Magnoflorine also enhanced the inhibitory effect of luteolin on MDA‐MB‐231 cells. Magnoflorine significantly inhibited CYP3A activity with the IC50 of 18.99 μM. Magnoflorine prolonged the system exposure, enhanced the metabolic stability, and enhanced the anti‐tumor effect of luteolin through inactivating CYP3A.

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Matrine inhibits invasion and migration of gallbladder cancer via regulating the PI3K/AKT signaling pathway

Mo,

Li,

Zhang

et al. 2024

Naunyn-Schmiedeberg's Arch Pharmacol

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Gallbladder cancer (GBC) is a common malignant cancer in the biliary system, which poses a serious threat to human health. It is urgent to explore ideal drugs for the treatment of GBC. Matrine is the main active ingredient of sophora avescentis, with a wide range of biological activities encompassing antiin ammatory, antiviral, immunomodulatory and anti-tumor. However, the underlying mechanism by which Matrine treats GBC is still unclear. The purpose of this study is to investigate the anti-tumor effects of Matrine on GBC in vivo and in vitro, and to clarify the potential regulatory mechanisms. Here, in this primer, we found that Matrine has a signi cant killing effect on GBC through CCK8 and ow cytometry, including arrest of cell cycle, inhibition of GBC cell, and induction of apoptosis. Further studies in vivo con rmed that the inhibitory function of Matrine on tumor growth in NOZ xenografted nude mouse. At the same time, Matrine also signi cantly suppressed the migration and invasion of GBC cells through scratch and Transwell experiments. In addition, by detecting the mRNA and protein levels of epithelialmesenchymal transition (EMT) and matrix metalloproteinases, Matrine furtherly substantiated the suppression of invasion and migration of GBC. From a mechanistic perspective, Matrine effectively decreased the abundance of p-PI3K and p-AKT protein in vivo and in vitro. More importantly, PI3K activator (740 Y-P) antagonized the anti-tumor effect of Matrine, while PI3K inhibitor (LY294002) increased the sensitivity of Matrine for GBC. Based on the above ndings, we conclude that Matrine inhibits the invasion and migration of GBC by regulating PI3K/AKT signaling pathway. Our results indicate the crucial role and regulatory mechanism of Matrine in suppressing the growth of GBC, which provides a theoretical basis for Matrine to be a candidate drug for the treatment and research of GBC.Cell culture GBC-SD cell line, a human GBC cell line, was purchased from Procell (Wuhan, China, Cat. No. CL-0085), while NOZ cell line (Cat. No. MZ-2106) of human GBC and HGBEC cell line (Cat. No. MZ-3197) of human gallbladder epithelial immortalized was both obtained from Ningbo, China. Whelab Bioscience Limited Corporation (Shanghai, China, Cat. No. C1546) provided SGC-996 cell line of the other human GBC. NOZ cells were cultured in DMEM medium containing 10% concentrations of fetal bovine serum (FBS, Wisent, Cat. No. 085-150), 100 U/ml penicillin (Beyotime, Cat. No. C0222), and 100 µg/ml streptomycin (Beyotime, Cat. No. C0222), while SGC-996 and GBC-SD cells were maintained in PRMI 1640 complete medium. The specialized medium was used for culturing HGBEC cells. All cells were cultured at 37 ℃ with 5% carbon dioxide. CCK8 assayCell viability was evaluated according to Cell Counting Kit-8 (MedChemExpress, Cat. No. HY-K0301) provided by the vender. The cells (HGBEC, GBC-SD, NOZ and SGC-996) were seeded in 96-well plates overnight and treated with different concentrations of Matrine (0-80 µM) for 12-72 hours, or treated with LY294002 (0-8...

show abstract

Adjunctive effect of compound Kushen injection for cancer: An overview of systematic reviews

Cited by 14 publications

References 25 publications

Efficacy and Safety of Compound Kushen Injection for Advanced Colorectal Cancer: A Systematic Review and Meta-Analysis of Randomized Clinical Trials with Trial Sequential Analysis

Efficacy and Safety of Compound Kushen Injection for Advanced Colorectal Cancer: A Systematic Review and Meta-Analysis of Randomized Clinical Trials with Trial Sequential Analysis

Pharmacokinetic study of the interaction between luteolin and magnoflorine in rats

Matrine inhibits invasion and migration of gallbladder cancer via regulating the PI3K/AKT signaling pathway

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