期刊：
FRONTIERS IN BIOSCIENCE-LANDMARK,2022年27(12) ISSN：2768-6701
通讯作者：
Tian, X.
作者机构：
[Wu, Ruoxia] School of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Hunan, Changsha, 410208, China;[Zhou, Ting] School of Pharmacy, Hunan University of Chinese Medicine, Hunan, Changsha, 410208, China;[Xiong, Jiaqing] Teaching and Research Section of Traditional Chinese Medicine Surgery, First Hospital of Hunan University of Chinese Medicine, Hunan, Changsha, 410021, China;[Tian, Xuefei; Zhang, Zhen] College of Integrated Traditional Chinese and Western Medicine, Hunan University of Chinese Medicine, Hunan, Changsha, 410208, China;[Tian, Sha] Department of Internal Medicine, College of Integrated Traditional Chinese and Western Medicine, Hunan University of Chinese Medicine, Hunan, Changsha, 410208, China
通讯机构：
[Tian, X.] C;College of Integrated Traditional Chinese and Western Medicine, Hunan, China
期刊：
Frontiers in Pain Research,2022年3:925013 ISSN：2673-561X
作者机构：
[Yan, Zhaobo; MuRong, Zhimiao; Zhong, Huan; Liu, Mailan; Liu, Mi] College of Acupuncture and Moxibustion, Hunan University of Chinese Medicine, China;[Huo, Bixiu] Hospital of Chengdu University of Traditional Chinese Medicine, China;[Yi, Chun] Department of Pathology, Hunan University of Chinese Medicine, China
关键词：
Acupuncture1;Cancer-induced bone pain2;meta-analysis3;Cancer pain4;A systematic review5
摘要：
Background: Cancer-induced bone pain (CIBP) is a special type of cancer pain and lacks safe and effective treatments. Acupuncture is a potentially valuable treatment for CIBP, studies evaluating the effect of acupuncture on CIBP have increased significantly, but the safety and efficacy of acupuncture to control CIBP remains controversial. Objective: To provide the first meta-analysis to evaluate the safety and efficacy of acupuncture in CIBP management. Data Sources: CNKI, CBM, Wanfang, VIP Database, PubMed, Embase, and Cochrane Library were searched from their inception until 1 June 2022. Study Selection: RCTs with primary bone tumor patients or other types of primary cancer companied by bone metastases as the research subjects and to evaluate the efficacy of acupuncture treatment alone or combined with the control treatment were included. Meanwhile, RCTs should choose the pain score as the primary outcome and pain relief rate, frequency of breakthrough pain, analgesic onset time, analgesia duration, quality of life, and adverse events as reference outcomes. Data Collection and Analysis: We designed a data-extraction form that was used to extract key information from the articles. Data extraction study evaluation was conducted independently by two reviewers, and a third reviewer would resolve any disagreements. The risk of bias was assessed by the Cochrane Collaboration's tool for assessing the risk bias. The quality of the evidence for main outcomes was evaluated by the GRADE system. Mean differences (MD), relative risk (RR), and 95% confidence intervals (CIs) were calculated. The forest plots were performed using the Review Manager Software (5.3 version). Subgroup analysis was used to investigate the possible sources of potential heterogeneity. Descriptive analysis was performed in case of unacceptable clinical heterogeneity. Results: Thirteen RCTs (with 1,069 patients) were included, and all studies were at high risk of bias owing to lack of blinding or other bias. Eleven studies evaluated the effectiveness of acupuncture as a complementary therapy, and showed that acupuncture plus control treatment (compared with control treatment) was connected with reduced pain intensity (MD = −1.34, 95% CI −1.74 to −0.94; Q < 0.1; I2 = 98%, P < 0.01). Subgroup analyses based on acupoints type partly explain the potential heterogeneity. The results also showed that acupuncture plus control treatment (compared with control treatment) was connected with relieving pain intensity, increasing the pain relief rate, reducing the frequency of breakthrough pain, shortening analgesic onset time, extending the analgesic duration, and improving the quality of life. We have no sufficient evidence to prove the effectiveness of acupuncture alone. Four RCTs reported only adverse events related to opioids' side effects. Evidence was qualified as “very low” because of low methodological quality, considerable heterogeneity, or a low number of included studies. Conclusion: Acupuncture has a certain effect as a complementary therapy on pain management of CIBP, which not only mitigates the pain intensity but also improves the quality of life and reduces the incidence of opioids' side effects, although the evidence level was very low. In future, a larger sample size and rigorously designed RCTs are needed to provide sufficient evidence to identify the efficacy and safety of acupuncture as a treatment for CIBP.
作者机构：
The First Hospital of Hunan University of Chinese Medicine, Hunan University of Chinese Medicine;College of Integrated Chinese and Western Medicine, Hunan Key Laboratory of Translational Research in Formulas and Zheng of Traditional Chinese Medicine, Hunan University of Chinese Medicine;Department of Preventive Dentistry, Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangzhou Medical University;Department of Physiology, Hunan University of Chinese Medicine;State Key Laboratory of Quality Research in Chinese Medicine, Macau Institute For Applied Research in Medicine and Health, Macau University of Science and Technology
关键词：
Hepatocellular carcinoma;Xihuang pills;Apoptosis;Antitumour;Phosphoinositide 3-kinase/protein kinase-B/mechanistic target of rapamycin pathway
摘要：
BACKGROUND The phosphoinositide 3-kinase/protein kinase-B/mechanistic target of rapamycin（PI3K/Akt/mTOR） signalling pathway is crucial for cell survival, differentiation, apoptosis and metabolism. Xihuang pills（XHP） are a traditional Chinese preparation with antitumour properties. They inhibit the growth of breast cancer, glioma, and other tumours by regulating the PI3K/Akt/mTOR signalling pathway. However, the effects and mechanisms of action of XHP in hepatocellular carcinoma（HCC） remain unclear. Regulation of the PI3K/Akt/mTOR signalling pathway effectively inhibits the progression of HCC. However, no study has focused on the XHPassociated PI3K/Akt/mTOR signalling pathway. Therefore, we hypothesized that XHP might play a role in inhibiting HCC through the PI3K/Akt/mTOR signalling pathway.AIM To confirm the effect of XHP on HCC and the possible mechanisms involved.METHODS The chemical constituents and active components of XHP were analysed using ultra-performance liquid chromatography-quadrupole time of flight mass spectrometry（UPLC-Q-TOF-MS）. Cellbased experiments and in vivo xenograft tumour experiments were utilized to evaluate the effect of XHP on HCC tumorigenesis. First, SMMC-7721 cells were incubated with different concentrations of XHP（0, 0.3125, 0.625, 1.25, and 2.5 mg/mL） for 12 h, 24 h and 48 h. Cell viability was assessed using the CCK-8 assay, followed by an assessment of cell migration using a wound healing assay.Second, the effect of XHP on the apoptosis of SMMC-7721 cells was evaluated. SMMC-7721 cells were stained with fluorescein isothiocyanate and annexin V/propidium iodide. The number of apoptotic cells and cell cycle distribution were measured using flow cytometry. The cleaved protein and mRNA expression levels of caspase-3 and caspase-9 were detected using Western blotting and quantitative reverse-transcription polymerase chain reaction（RT-qPCR）, respectively.Third, Western blotting and RT–qPCR were performed to confirm the effects of XHP on the protein and mRNA expression of components of the PI3K/Akt/mTOR signalling pathway.Finally, the effects of XHP on the tumorigenesis of subcutaneous hepatocellular tumours in nude mice were assessed.RESULTS The following 12 compounds were identified in XHP using high-resolution mass spectrometry:Valine, 4-gingerol, myrrhone, ricinoleic acid, glycocholic acid, curzerenone, 11-keto-β-boswellic acid, oleic acid, germacrone, 3-acetyl-9,11-dehydro-β-boswellic acid, 5β-androstane-3,17-dione, and 3-acetyl-11-keto-β-boswellic acid. The cell viability assay results showed that treatment with 0.625mg/mL XHP extract decreased HCC cell viability after 12 h, and the effects were dose-and timedependent. The results of the cell scratch assay showed that the migration of HCC cells was significantly inhibited in a time-dependent manner by the administration of XHP extract（0.625mg/mL）. Moreover, XHP significantly inhibited cell migration and resulted in cell cycle arrest and apoptosis. Furthermore, XHP downregulated the PI3K/Akt/mTOR signalling pathway, which activated apoptosis executioner proteins（e.g., caspase-9 and caspase-3）. The inhibitory effects of XHP on HCC cell growth were determined in vivo by analysing the tumour xenograft volumes and weights.CONCLUSION XHP inhibited HCC cell growth and migration by stimulating apoptosis via the downregulation of the PI3K/Akt/mTOR signalling pathway, followed by the activation of caspase-9 and caspase-3.Our findings clarified that the antitumour effects of XHP on HCC cells are mediated by the PI3K/Akt/mTOR signalling pathway, revealing that XHP may be a potential complementary therapy for HCC.
期刊：
Evidence-Based Complementary and Alternative Medicine,2022年2022 ISSN：1741-427X
通讯作者：
Hu, R.
作者机构：
[Hu, Ruicheng; Wang, Lile] Hunan Normal Univ, Hunan Prov Peoples Hosp, Dept Resp Med, Affiliated Hosp 1, Changsha 410016, Peoples R China.;[Dai, Aiguo] Hunan Univ Chinese Med, Med Sch, Dept Resp Dis, Changsha 410208, Peoples R China.
通讯机构：
Department of Respiratory Medicine, Hunan Provincial People's Hospital, The First-affiliated Hospital of Hunan Normal University, Changsha, China
摘要：
<i>Objective</i>. Non-small-cell lung cancer (NSCLC) is one of the most lethal cancers. Although cisplatin-based chemotherapies have been regarded as a promising treatment approach, cisplatin resistance still remains one of the major clinical challenges. Curcumin, a naturally occurring polyphenol, has been proved to increase chemotherapeutic efficiency of NSCLC cells. However, the role of curcumin in cisplatin-resistant NSCLC cells has been rarely investigated. This study aims to investigate whether curcumin enhances cisplatin sensitivity of human NSCLC cells and its underlying mechanisms. <i>Method</i>. A549/DDP and H1299/DDP cells were treated by DDP or/and curcumin before cell viability, and apoptosis were determined by using a CCK-8 assay and flow cytometer. The expressions of apoptosis and ER stress-related proteins, including cleaved caspase-3, cleaved PARP, CHOP, GRP78, XBP-1, ATF6, and caspase-4, were measured by the qPCR and western blotting. After cotreatment by DDP and curcumin, A549/DDP and H1299/DDP cells were further treated by the ER stress inhibitor, salubrinal (20 <i>μ</i>m), after which the cell apoptosis and viability were detected. <i>Result</i>. Treatment by DDP and curcumin can substantially decrease cell viability, while can increase the cell apoptosis rate, elevate mRNA and protein expressions of apoptosis and ER stress-related proteins, compared with cells treated by DDP or curcumin alone. Salubrinal treatment can counteract the suppressive effect of DDP and curcumin on cell viability and decrease the cell apoptosis of A549/DDP and H1299/DDP cells. <i>Conclusion</i>. Curcumin can increase the sensitivity of NSCLC to cisplatin through an ER stress pathway and thus can be served as one of the molecular targets for overcoming the cisplatin resistance.
作者：
Liu, Yong-Ping;Lei, Jian;Yin, Ming-Ming;Chen, Yi
期刊：
Anti-Cancer Agents in Medicinal Chemistry,2022年22(13):2448-2457 ISSN：1871-5206
通讯作者：
Liu, Y.-P.
作者机构：
[Chen, Yi; Liu, Yong-Ping] Hunan Univ Chinese Med, Sch Med, Dept Physiol, 300 Xueshi Rd,Hanpu Sci & Educ Pk, Changsha 410208, Hunan, Peoples R China.;[Lei, Jian] Hunan Univ, Coll Chem & Chem Engn, State Key Lab Chemo Biosensing & Chemometr, Changsha 410082, Hunan, Peoples R China.;[Yin, Ming-Ming] Hunan Univ Chinese Med, Coll Integrated Tradit Chinese & Western Med, Changsha 410208, Hunan, Peoples R China.
通讯机构：
Department of Physiology, School of Medicine, Hunan University of Chinese Medicine, 300 Xueshi Road, Hanpu Science and Education Park, Yuelu District Hunan, Changsha, China
关键词：
Metal complex;necroptosis inducer;anti-cancer;triple-negative breast cancer;ROS;oxidative stress.
摘要：
Aim: This study aimed to investigate the anticancer effect and the underlying mechanisms of organoantimony (III) fluoride on MDA-MB-231 human breast cancer cells. Methods: Five cancer and one normal cell line were treated with an organoantimony (III) compound 6-cyclohexyl-12- fluoro-5,6,7,12-tetrahydrodibenzo[c,f][1,5]azastibocine (denoted as C4). The cell viability was detected by MTT assay. Induction of cell death was determined by Hoechst 33342/PI staining and Annexin-V/PI staining. The effect of C4 on the necroptotic relative protein was determined by Western blot analysis. Results: Among the five cancer cell lines, C4 decreased the viability of MDA-MB-231, MCF-7 and A2780/cisR, and showed less toxicity on normal human embryonic kidney cells. In breast cancer cell line MDA-MB-231, the C4 treatment induced necrotic cell death as well as LDH release in a time- and dose-dependent manner. Moreover, C4 could increase the expression of phosphorylated RIPK3 and MLKL proteins. Overall, the C4 treatment resulted in the reduction of mitochondrial transmembrane potential and accumulation of ROS in MDA-MB-231 cells. Conclusion: C4-induced necroptosis could be ascribed to glutathione depletion and ROS elevation in MDA-MB-231 cells. Our findings illustrate C4 to be a potential necroptosis inducer for breast cancer treatment.
