Abstract. The underlying mechanism of the antitumor activity of Huaier polysaccharide (HP) remains to be explored. The present study aimed to investigate the inhibitory effect of HP on hepatocellular carcinoma (HCC) cells, and to explore the possible mechanisms of its anticancer effect. Cell viability was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, while apoptotic nuclear changes were observed using Hoechst 33258 staining. The distribution of cell cycle and apoptosis were analyzed by flow cytometry, and western blotting was used to test the apoptotic pathways. Apoptosis and mitogen-activated protein kinase (MAPK) inhibitors were used to investigate the mechanism of apoptosis. HP triggered cell cycle arrest and apoptosis in HepG2 and Huh7 cells. Both the extrinsic and intrinsic apoptotic pathways were activated after HP treatment. Furthermore, HP enhanced the three major MAPK pathways (extracellular signal-regulated kinase, c-Jun N-terminal kinase and p38 MAPK) and inhibited the AKT/mechanistic target of rapamycin signaling pathway in HCC cells. Notably, the inactivation of p38 MAPK impaired the HP-induced cell death. HP exerted its antitumor effect on HCC cells through the regulation of the expression of the apoptosis-related proteins B-cell lymphoma (Bcl)-2, Bcl-2-associated X protein and survivin. The present study provides evidence that HP induces apoptosis in HCC cells and demonstrated the role of p38 MAPK in HP-triggered cancer cell death. IntroductionLiver cancer, particularly hepatocellular carcinoma (HCC), is one of the most common human malignancies with poor long-term survival rates (1-3). Although liver transplantation, hepatectomy and local therapy are potentially curative therapies in the early stages of HCC (4,5), the majority of patients, who are usually diagnosed at an advanced stage, must rely mainly on traditional chemotherapies (6,7). Currently, there is no proven effective conventional systemic chemotherapy for patients with advanced HCC (7). Therefore, novel therapeutic agents with high efficacy are urgently required for the clinical treatment of advanced HCC.Trametes robiniophila Murr (Huaier) is a type of fungus that exists in China, and previous chemical analyses revealed that Huaier consists mainly of polysaccharide (8). Recent studies have noticed that Huaier polysaccharide (HP) exerts a pro-apoptotic effect on the cells of a variety of human cancers, including breast cancer (9,10), hepatocarcinoma (11-14), lung adenocarcinoma (15) and ovarian cancer (16). In addition, Huaier and HP suppress cancer cell metastasis and motility (12,16,17), exhibit anti-angiogenic activity and enhance the host immune system function (11,14,18). Together, these data indicate that HP exhibits promising results against cancer in pre-clinical trials.The use of Huaier has been approved by the Chinese Food and Drug Administration for the clinical treatment of patients with malignant tumors (China Food and Drug Administration approval number, Z20000109; http://app1.sfda.gov.cn...
Abstract. The incidence of oral squamous cell carcinoma (OSCC) is continuously increasing while its survival rate has not notably improved. There is a pressing need for improved understanding of the genetic regulation of OSCC tumorigenesis and progression. In this study, the function of miR-448 in the regulation of OSCC growth and its putative target were thoroughly analyzed in vitro. The expression of miR-448 was detected in human OSCC specimens and OSCC cell lines (Cal-27 and Scc-9) by reverse transcription-quantitative polymerase chain reaction. The function of miR-448 was investigated in Cal-27 cells transfected with miR-448 inhibitor, and its putative target determined using a luciferase reporter assay. MTT and wound healing assays and flow cytometry were used to evaluate the effects of miR-448 on OSCC proliferation, metastasis and apoptosis. The level of miR-448 was significantly elevated in human OSCC tissues and the Cal-27 cell line. Suppression of miR-448 expression attenuated cell proliferation and migration, and induced apoptosis of Cal-27 cells. Furthermore, miR-448 bound with the 3'-untranslated region of metallophosphoesterase domain containing 2 (MPPED2) mRNA, thereby reducing the MPPED2 protein level. Thus, it appears that miR-448 acts as a tumor inducer, causing OSCC growth by inhibiting the expression of its target MPPED2.These results demonstrate that miR-448 plays a critical role in OSCC tumorigenesis, and is a potential therapeutic target.
Background Oral cancer (OC) poses a threat to human health and imposes a heavy burden on countries. We assessed the burden imposed by OC on Asian nations from 1990 to 2019 based on gender and age. Methods We collected oral cancer data from the 2019 Global Burden of Disease study from 1990 to 2019 in 45 Asian countries and territories. Annual case data and age-standardised rates (ASRs) were used to investigate the incidence, mortality, and disability-adjusted life-years (DALYs) of OC based on age and gender from 1990 to 2019 in 45 Asian countries and territories. Estimated annual percentage changes (EAPCs) were used to assess incidence rate, mortality, and trends in DALYs. Results The age-standardised incidence rate (ASIR) of OC increased from 1990 to 2019 with an EAPC of 0.32 (95% CI, 0.19–0.46), and the age-standardised death rate of OC remained stable at an EAPC of 0.08 (95%CI, from -0.06 to 0.21). The age-standardised DALYs of OC decreased at an EAPC of -0.16 (95%CI, from -0.30 to -0.02). The proportion of patients older than 70 years increased yearly in terms of incidence, mortality, and DALYs from 1990 to 2019. Of the DALYs, smoking was the main contributor in the Asian regions, and the largest contributor to DALYs in most Asian regions. Other contributors were alcohol use and chewing tobacco. Conclusion Although the burden of OC was declining in Asia, South Asia remained the region with the highest burden. OC caused the greatest burden in Pakistan, Taiwan China, and India. Therefore, measures should be taken to reduce the burden of oral cancer in high-risk regions and countries with attributable risk factors.
Background: Oral cancer (OC) is a common tumour that poses a threat to human health and imposes a heavy burden on countries. This study assessed the burden imposed by OC on the 10 most populous countries from 1990 to 2019 on the basis of gender, age and socio-demographic index. Methods: Data on incidence, mortality, disability-adjusted life years (DALY) and corresponding age-standardised rates (ASR) for OC in the 10 most populous countries from 1990 to 2019 were derived from the Global Burden of Disease Study 2019. Estimated annual percentage changes were calculated to assess the trends of morbidity, mortality and DALY. The indicator that served as a proxy for survival rate was the supplement of mortality-to-incidence ratio (SMIR) (1 − (M/I)). Results: The number of new cases, deaths and DALY have increased in all 10 countries in the past 30 years. Trends in age-standardised incidence rates (ASIR), age-standardised mortality rate (ASMR) and age-standardised DALY for OC in the 10 most populous countries varied. The SMIR increased in all countries, with most countries having an SMIR between 30% and 50%. In 2019, the United States had the highest SMIR at 76%, whereas Russia had the lowest at 21.7%. Incidence and mortality were close between male and female subjects in Japan, Indonesia, Mexico, India, Bangladesh and Pakistan. The incidence and mortality in male subjects in the United States, Russia, China and Brazil were two or more times those of female subjects. Gender difference was highest among patients aged 40–69 years. Conclusion: Trends and gender differences in ASIR, ASMR and age-standardised DALY for OC vary in the 10 most populous countries. Government cancer programs are often expensive to run, especially in countries with large populations. Policy makers need to take these differences into account when formulating policies.
This study reports the risk factors, trends, and burden of cancer in China from 1990 to 2019 from the Global Burden of Diseases. The incidence, mortality, and DALY of all cancers in China for the past 30 years were analyzed. In 2019, the age-standardized rates (ASRs) of cancer incidence, mortality, and DALY in China were 232.42/100 000, 136.72/100 000, and 3288.22/100 000, respectively. The five cancers with the highest age-standardized incidence rates were lung, stomach, colorectal, breast, and prostate cancers. From 1990 to 2019, the number of new cancer cases, deaths, and DALY increased by 168.78%, 86.89%, and 51.20%, respectively. The ASR increased by 22.21% for incidence and decreased by 19.01% and 27.19% for mortality and DALY, respectively, and their corresponding average annual percent change values were 0.71, -0.80, and -1.26, respectively. The main risk factors for cancer in China were smoking, air pollution, dietary factors, and alcohol use. From 1990 to 2019, the cancer incidence rate was on the rise, and cancer mortality and DALY rates were declining; however, these characteristics vary by cancer site. Therefore, current prevention strategies should be reoriented, and specific strategies for cancers in different sites should be established to prevent the increase in cancer cases.
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