Fei-Liu-Ping ointment inhibits lung cancer growth and invasion by suppressing tumor inflammatory microenvironment

BACKGROUND: Lung cancer is one of the leading causes of cancer-related mortality worldwide. Conventional chemotherapy and radiotherapy are the primary therapeutic methods for lung cancer with the use of combination therapies gaining popularity. The frequency and duration of treatment, as well as, managing lung cancer by targeting multiple aspects of cancer biology is often limited by toxicity to the patient. There are many naturally occurring anticancer agents that have a high degree of efficacy and low toxicity, offering a viable and safe approach for the treatment of lung cancer. The herbs traditionally used in Chinese medicine for anticancer treatment offer great potential to enhance the efficacy of conventional therapy. In this study, we evaluated the synergistic effects of Fei-Liu-Ping (FLP) ointment in treating lung cancer; a known anticancer Chinese herbal based formula. METHODS: In this study, A549 human lung carcinoma cell line and Lewis lung carcinoma xenograft mouse model were used. In addition, we utilized an in vitro co-culture system to simulate the tumor microenvironment in order to evaluate the molecular mechanisms of FLP treatment. RESULTS: FLP treatment significantly inhibited tumor growth in the Lewis lung xenograft by 40 percent, compared to that of cyclophosphamide (CTX) of 62.02 percent. Moreover, combining FLP and CTX inhibited tumor growth by 83.23 percent. Upon evaluation, we found that FLP treatment reduced the concentration of serum pro-inflammatory cytokines IL-6, TNF-α, and IL-1β. In addition, we also found an improvement in E-cadherin expression and inhibition of N-cadherin and MMP9. We found similar findings in vitro when we co-cultured A549 cells with macrophages. FLP treatment inhibited A549 cell growth, invasion and metastasis, in part, through the regulation of NF-κB and altering the expression of E-cadherin, N-cadherin, MMP2 and MMP9. CONCLUSIONS: FLP exerts anti-inflammatory properties in the tumor microenvironment, which may contribute to its anticancer effects. FLP treatment may be a promising therapy for inflammation associated lung cancer treatment alone, or in combination with conventional therapies and may prevent lung cancer metastasis

Compound Kushen Injection suppresses human breast cancer stem-like cells by down-regulating the canonical Wnt/β-catenin pathway

<p>Abstract</p> <p>Background</p> <p>Cancer stem cells (CSCs) play an important role in cancer initiation, relapse and metastasis. To date, no specific medicine has been found to target CSCs as they are resistant to most conventional therapies and proliferate indefinitely. Compound Kushen Injection (CKI) has been widely used for cancer patients with remarkable therapeutic effects in Chinese clinical settings for many years. This study focused on whether CKI could inhibit MCF-7 SP cells in vitro and in vivo.</p> <p>Methods</p> <p>The analysis of CKI on SP population and the main genes of Wnt signaling pathway were studied first. Then we studied the tumorigenicity of SP cells and the effects of CKI on SP cells in vivo. The mice inoculated with 10,000 SP cells were randomly divided into three groups (6 in each group) and treated with CKI, cisplatin and saline (as a control) respectively for 7 weeks. The tumor formation rates of each group were compared. The main genes and proteins of the Wnt signaling pathway were analyzed by RT-PCR and western blot.</p> <p>Results</p> <p>CKI suppressed the size of SP population (approximately 90%), and down-regulated the main genes of Wnt signaling pathway. We also determined that MCF-7 SP cells were more tumorigenic than non-SP and unsorted cells. The Wnt signaling pathway was up-regulated in tumors derived from SP cells compared with that in tumors from non-SP cells. The tumor formation rate of the CKI Group was 33% (2/6, <it>P </it>< 0.05), and that of Cisplatin Group was 50%(3/6, <it>P </it>< 0.05), whereas that of the Control Group was 100% (6/6).The RT-PCR and western blot results indicated that CKI suppressed tumor growth by down-regulating the Wnt/β-catenin pathway, while cisplatin activated the Wnt/β-catenin pathway and might spare SP cells.</p> <p>Conclusions</p> <p>It suggested that CKI may serve as a novel drug targeting cancer stem-like cells, though further studies are recommended.</p

Targeting Signal Transducer and Activator of Transcription 3 for Colorectal Cancer Prevention and Treatment with Natural Products

Signal transducers and activators of transcription 3 (STAT3), a transcription factor, plays key role in regulating the signal transduction events mediated by cytokines and growth factors. STAT3 is involved in many activities including survival, proliferation, differentiation, and apoptosis. Persistent activation of STAT3 has been demonstrated to be closely correlated to tumor cell proliferation, apoptosis, invasion, metastasis, and angiogenesis. Recent studies indicate that treatment with STAT3 inhibitor or silencing the expression of STAT3 can significantly reduce the progression/incidence of colorectal cancer (CRC), partly through regulating inflammation. Therefore, STAT3 offers a promising therapy. This review evaluates the evidence linking STAT3 with CRC development and analyzes the molecular mechanisms involved, specifically focusing on discussing the roles of natural products or herbal medicines on CRC progression by targeting STAT3. STAT3 activity suppresses tumor development and progression in part by regulating inflammation

A nomogram for predicting severe myelosuppression in small cell lung cancer patients following the first-line chemotherapy

Abstract This study aimed at establishing and validating a nomogram to predict the probability of severe myelosuppression in small cell lung cancer (SCLC) patients following the first-line chemotherapy. A total of 179 SCLC cases were screened as the training group and another 124 patients were used for the validation group. Predictors were determined by the smallest Akaike’s information criterion (AIC) in multivariate logistic regression analysis, leading to a new nomogram. The nomogram was validated in both training and validation groups and the predicting value was evaluated by area under the receiver operating characteristics (ROC) curve (AUC), calibration curve, and decision curve analysis (DCA). Age and tumor staging were extracted as predictors to establish a nomogram, which displayed the AUC values as 0.725 and 0.727 in the training and validation groups, respectively. This nomogram exhibited acceptable calibration curves in the two groups and its prediction added more net benefits than the treat-all scheme and treat-none scheme if the range of threshold probability in the DCA was between 15 and 60% in the training and validation groups. Therefore, the nomogram objectively and accurately predict the occurrence of severe myelosuppression in SCLC patients following the first-line chemotherapy

Cinobufacini Injection Improves the Efficacy of Chemotherapy on Advanced Stage Gastric Cancer: A Systemic Review and Meta-Analysis

Gastric cancer has a high morbidity and mortality. Chemotherapy regimens are routine advanced stage gastric cancer (AGC) treatment protocols, but most of these drugs have side-effects such as myelosuppression and gastrointestinal disorders. Cinobufacini, an extractive from TCM, could suppress cell proliferation and inhibit gastric cancer. In this study, we comprehensively reviewed the literature on the efficacy comparison between Cinobufacini injection combined with chemotherapy and chemotherapy solely used in AGC treatment. We extracted data for from six electronic databases to evaluate the efficacy of Cinobufacini injection on AGC patients. Twelve studies with a total of 853 patients were finally included in our study. The results indicated that Cinobufacini injection could increase response rate and disease control rate of chemotherapy on AGC, improve the life quality of AGC patients, increase leukocytes, improve anemia, improve hand-foot syndrome induced by chemotherapy, and relieve cancer pain. This study has its own limitations that prevented us from drawing a definite conclusion and more well-designed clinical trials of TCM are needed

Complementary and Alternative Medicine for Cancer Pain: An Overview of Systematic Reviews

Background and Objective. Now with more and more published systematic reviews of Complementary and Alternative Medicine (CAM) on adult cancer pain, it is necessary to use the methods of overview of systematic review to summarize available evidence, appraise the evidence level, and give suggestions to future research and practice. Methods. A comprehensive search (the Cochrane Library, PubMed, Embase, and ISI Web of Knowledge) was conducted to identify all systematic reviews or meta-analyses of CAM on adult cancer pain. And the evidence levels were evaluated using GRADE approach. Results. 27 systematic reviews were included. Based on available evidence, we could find that psychoeducational interventions, music interventions, acupuncture plus drug therapy, Chinese herbal medicine plus cancer therapy, compound kushen injection, reflexology, lycopene, TENS, qigong, cupping, cannabis, Reiki, homeopathy (Traumeel), and creative arts therapies might have beneficial effects on adult cancer pain. No benefits were found for acupuncture (versus drug therapy or shame acupuncture), and the results were inconsistent for massage therapy, transcutaneous electric nerve stimulation (TENS), and Viscum album L plus cancer treatment. However, the evidence levels for these interventions were low or moderate due to high risk of bias and/or small sample size of primary studies. Conclusion. CAM may be beneficial for alleviating cancer pain, but the evidence levels were found to be low or moderate. Future large and rigor randomized controlled studies are needed to confirm the benefits of CAM on adult cancer pain

Topical Treatment with Xiaozheng Zhitong Paste (XZP) Alleviates Bone Destruction and Bone Cancer Pain in a Rat Model of Prostate Cancer-Induced Bone Pain by Modulating the RANKL/RANK/OPG Signaling

To explore the effects and mechanisms of Xiaozheng Zhitong Paste (XZP) on bone cancer pain, Wistar rats were inoculated with vehicle or prostate cancer PC-3 into the tibia bone and treated topically with inert paste, XZP at 15.75, 31.5, or 63 g/kg twice per day for 21 days. Their bone structural damage, nociceptive behaviors, bone osteoclast and osteoblast activity, and the levels of OPG, RANL, RNAK, PTHrP, IGF-1, M-CSF, IL-8, and TNF-α were examined. In comparison with that in the placebo group, significantly reduced numbers of invaded cancer cells, decreased levels of bone damage and mechanical threshold and paw withdrawal latency, lower levels of serum TRACP5b, ICTP, PINP, and BAP, and less levels of bone osteoblast and osteoclast activity were detected in the XZP-treated rats (P<0.05). Moreover, significantly increased levels of bone OPG but significantly decreased levels of RANL, RNAK, PTHrP, IGF-1, M-CSF, IL-8, and TNF-α were detected in the XZP-treated rats (P<0.05 for all). Together, XZP treatment significantly mitigated the cancer-induced bone damage and bone osteoclast and osteoblast activity and alleviated prostate cancer-induced bone pain by modulating the RANKL/RANK/OPG pathway and bone cancer-related inflammation in rats