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This manuscript aims to investigate the effects of resibufogenin on the proliferation, migration and invasion of human hepatocellular carcinoma cells and its related mechanisms. MTT assay was used to determine the inhibitory effect of resibufogenin on the growth of four hepatocellular carcinoma cells in vitro. Wound-healing assay and Transwell assay were used to evaluate the migration and invasion ability of resibufogenin on MHCC-97H cells. Western blot assay was used to detect the expression of migration and invasion related proteins in MHCC-97H cells treated with different concentrations of resibufogenin. The results showed that resibufogenin significantly inhibited the proliferation of hepatocellular carcinoma cells in vitro. The half maximal inhibitory concentration (IC50) values on MHCC-97H, HepG2, SK-Hep-1 and Huh-7 cells were 0.55 ± 0.06, 2.83 ± 0.24, 5.25 ± 0.49, 14.89 ± 2.28 μmol·L-1, respectively. Resibufogenin also suppressed the migration and invasion of MHCC-97H cells in a concentration-dependent manner. The protein expression of integrin α2, integrin α6, integrin β1, N-cadherin, matrix metalloproteinase 2 (MMP2) and transcription factor Twist in MHCC-97H cells were decreased significantly with the increase of the concentration of resibufogenin, while the protein expression of E-cadherin increased. In addition, we found that p-PI3K/PI3K and p-AKT/AKT ratios were significantly reduced after treatment with resibufogenin. In conclusion, resibufogenin can inhibit the proliferation, migration and invasion of hepatocellular carcinoma MHCC-97H cells in vitro, which is related to the regulation of intracellular migration and invasion protein expression and PI3K/AKT signaling pathway.
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In this study, we investigated the inhibitory effects of bufalin on proliferation, migration and invasion of PC3 cells in vitro, and preliminarily explored the molecular mechanism of epithelial-mesenchymal transformation (EMT) inhibited by bufalin. The viability of PC3 cells was evaluated by MTT assay, and the migration and invasion abilities of PC3 cells were detected by wound healing and Transwell assay. Western blot was used to detect the expression of EMT and integrin family proteins. The results showed that the half maximal inhibitory concentration (IC50) value of bufalin against PC3 cells was 0.26 ± 0.03 μmol·L-1. After bufalin treatment, the migration rate of PC3 cells slowed down (P < 0.05), the number of PC3 cells passing through the microporous membrane decreased (P < 0.05), which indicated that bufalin could inhibit the proliferation, migration and invasion of PC3 cells in a concentration-dependent manner. We found that bufalin could affect the expression of EMT-related proteins,including up-regulation of E-cadherin and down-regulation of N-cadherin, β-catenin, matrix metalloproteinase 9 (MMP9), matrix metalloproteinase 2 (MMP2), c-myc and Snail. Bufalin also inhibited the expression of integrin family proteins, including integrin α2 (ITGA2), integrin β1 (ITGB1), integrin β3 (ITGB3), integrin β5 (ITGB5), Yes-associated protein/transcriptional coactivator with a PDZ-binding motif (YAP/TAZ) and integrin-linked kinase (ILK). In addition, bufalin could also inhibit the protein expression level of phospho-focal adhesion kinase (p-FAK)/FAK, phospho-steroid receptor coactivator (p-Src)/Src and phospho-protein kinase B (p-Akt)/Akt. These results suggested that bufalin might inhibit the proliferation, metastasis and invasion of prostate cancer PC3 cells through the FAK/Src/phosphoinositide 3-kinase (PI3K)/Akt pathway. Therefore, bufalin provides reference value for the development of therapeutic drugs for prostate cancer.
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Zanthoxyli Radix is a traditional Chinese medicine. It can be used for the treatment of wind-cold-dampness arthralgia, muscle and bone pain, fall fracture, hernia, sore throat, toothache and other diseases. Due to possessing many excellent and mild pharmacological properties, there are lots of reports about Zanthoxyli Radix worldwide. At present, more than 100 bioactive components have been extracted and purified from Zanthoxyli Radix. Nitidine chloride (NC), one of the most important alkaloids in Zanthoxyli Radix, has the activities of anti-tumor, anti-inflammation, anti-bacteria, etc. In this review, we summarize the chemical components of Zanthoxyli Radix, pharmacological activity and mechanism of action of NC to provide references for further research and utilization of Zanthoxyli Radix.
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We investigated the inhibitory effect and mechanism of action of bruceantin (BCT) on the proliferation, invasion and migration of non-small cell lung cancer (NSCLC) cells. The cytotoxic activity of BCT was measured by MTT assay; a colony forming assay, wound healing assay, and a Transwell assay were used to investigate the anti-proliferative, anti-migration, and anti-invasion effects, respectively; immunoblotting and RT-qPCR were used to detect the expression of related proteins, miRNA, and mRNA, respectively, that were involved in cell proliferation, migration, and invasion. Two gene prediction websites were used to predict the downstream target gene of miRNA. Our results show that BCT has a potent cytotoxic effect on NSCLC cell lines, with a half maximal inhibitory concentration (IC50) of BCT against H1299, PC-9, and A549 of 0.12 ± 0.02, 0.31 ± 0.20, and 2.07 ± 0.70 μmol·L-1, respectively. When H1299 cells were treated with 0.03, 0.15, and 0.75 μmol·L-1 BCT for 24 h, the proliferation, migration, and invasive ability were inhibited in a concentration-dependent manner. It is worth noting that the expression level of miRNAs related to cell migration and invasion, such as miR-29a-3p, miR-21-3p, miR-183-5p, and miR-34b-5p increased with the concentration of BCT, especially for miR-29a-3p. Using the two gene prediction websites, we predict that integrin β1 (ITGB1) may be the target gene of miR-29a-3p; immunoblot results further show that a variety of proteins related to cell proliferation, migration, and invasion, such as various proteins of the integrin family, β-catenin, p-Src, and vascular endothelial growth factor, all decreased in a concentration-dependent manner, among which the reduction of ITGB1 protein was the most obvious. RT-qPCR results showed that there was no change in ITGB1 mRNA expression. We speculate that BCT might inhibit the expression of ITGB1 protein by up-regulating miR-29a-3p independent of its mRNA level. The in-depth mechanism needs to be further explored. This study suggests that BCT has the potential for further development in the treatment of NSCLC.
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The incidence and mortality of chronic obstructive pulmonary disease (COPD) and lung cancer are increasing year by year, which are causing massive social and financial burdens around the world. An increasing number of investigations indicate the possibility of COPD transforming into lung cancer. The pathogenesis of these two diseases have some common aspects, such as epithelial-mesenchymal transition, chronic inflammation, DNA damage, impaired immune system, oxidative stress and tumor angiogenesis, which are heavily complicated. This review summarizes the epidemiological connection between COPD and lung cancer, the molecular-level transformation mechanism as well as the therapeutic strategy. Exploring the transformation mechanism and related signaling pathway of COPD to lung cancer can contribute to block the risk factors for the transformation and provide guidance for the novel drug development and drug therapy.
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Snow lotus is a medicinal plant with a wide range of pharmacological activities. It has been used to treat rheumatoid arthritis, cough with cold, stomach ache, dysmenorrhea, and altitude sickness in traditional medicine. This review summarizes the bioactive components in six species of snow lotus including flavonoids, lignans, phenolic compounds, phenylpropanoids, and sesquiterpenes present in Saussurea involucrate (SI), Saussurea obvallata (SO), Saussurea laniceps (SL), Saussurea medusa (SM), Saussurea stella (SS) and Saussurea tridactyla (ST). We review the pharmacological and related molecular mechanisms by which these components exert antineoplastic, anti-inflammatory, and antioxidant effects and promote lipid catabolism, and provide a reference for the future study of the traditional Chinese medicinal chemistry and pharmacological activities of snow lotus.
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<p><b>OBJECTIVE</b>To study the clinical characteristics and effects of immunoglobulin treatment in children with the different types of Guillain-Barré syndrome (GBS).</p><p><b>METHOD</b>Data of 108 patients hospitalized for GBS were retrospectively analyzed; 75 cases in this group were given acute high dose of gamma globulin (IVIG) 400 mg/(kg·d) intravenously for 5 d. Clinical and electrophysiological data and information on treatment and recovery of the children were collected during the follow-up and were analyzed.</p><p><b>RESULT</b>According to the clinical and electrophysiologic findings, 32 patients manifested acute inflammatory demyelinating polyradiculoneuropathy (AIDP), 34 had acute motor axonal neuropathy (AMAN), 3 had acute motor and sensory axonal neuropathy (AMSAN), 4 were inexcitable, 2 were unclassified. The clinical progress of the AMAN was faster than the AIDP group. Except for sensory nerve involvement, there was no significant difference in the clinical feature and severity. The mean time of the muscle strength began to recover was (5.59±3.63) days in the AIDP group and (7.21±4.68) days in the AMAN group after IVIG treatment. The time of the AIDP group was shorter than the AMAN group, but the difference was not statistically significant (t=-1.5702, P>0.05). The mean time of the muscle strength increased one grade was (8.88±4.39) days in the AIDP group and (12.67±8.35) days in the AMAN group. The difference was statistically significant (t=-2.3689, P<0.05). No patients in this group died. Follow-up data showed that the complete recovery time was not significantly different (t=0.2041, P>0.05).</p><p><b>CONCLUSION</b>The clinical progress of the AMAN was faster than the AIDP group. Besides sensory nerve involvement, there was no significant difference in the clinical feature and severity. The AIDP group's clinical recovery was faster than AMAN's after the immunoglobulin treatment. The two groups were not significantly different in long-term prognosis.</p>