The Curcumin Analog EF24 Inhibits Proliferation and Invasion of Triple-Negative Breast Cancer Cells by Targeting the Long Noncoding RNA HCG11/Sp1 Axis.

EF24, a curcumin analog, exerts a potent antitumor effect on various cancers. However, whether EF24 retards the progression of triple-negative breast cancer (TNBC) remains unclear. In this study, we explored the role of EF24 in TNBC and clarified the underlying mechanism. In a mouse model of TNBC xenograft, EF24 administration reduced the tumor volume, suppressed cell proliferation, promoted cell apoptosis, and downregulated long noncoding RNA human leukocyte antigen complex group 11 (HCG11) expression. In TNBC cell lines, EF24 administration reduced cell viability, suppressed cell invasion, and downregulated HCG11 expression. HCG11 overexpression reenhanced the proliferation and invasion of TNBC cell lines suppressed by EF24. The following mechanism research revealed that HCG11 overexpression elevated Sp1 transcription factor (Sp1) expression by reducing its ubiquitination, thereby enhanced Sp1-mediated cell survival and invasion in the TNBC cell line. Finally, the in vivo study showed that HCG11-overexpressed TNBC xenografts exhibited lower responsiveness in response to EF24 treatment. In conclusion, EF24 treatment reduced HCG11 expression, resulting in the degradation of Sp1 expression, thereby inhibiting the proliferation and invasion of TNBC cells.

Fatigue prevalence in men treated for prostate cancer: A systematic review and meta-analysis.

BACKGROUND: The side effects of prostate cancer (PCa) treatment are very prominent, with cancer-related fatigue (CRF) being the most common. Fatigue is a distressing symptom that interferes with daily functioning and seriously affects patient quality of life during, and for many years after, treatment. However, compared with other types of cancer, such as breast cancer, little is known about the prevalence of PCa-related fatigue. AIM: To determine the prevalence of CRF in patients with PCa. METHODS: A systematic search of EMBASE, PubMed, Web of Science, Cochrane Library, Chinese National Knowledge Infrastructure, WANFANG DATA, Technology Journal Database and the Chinese Biological Medical Database was conducted up to July 28, 2020. Included studies measured the incidence of PCa-related fatigue and differentiated fatigue outcomes (incidence) between treatment modalities and fatigue assessment times. In our meta-analysis, both fixed and random-effects models were used to estimate the pooled prevalence of PCa-related fatigue. Subgroup analyses were performed using treatment modalities and fatigue assessment times. Publication and sensitivity bias analyses were performed to test the robustness of the associations. RESULTS: Fourteen studies, involving 4736 patients, were eligible for the review. The pooled CRF prevalence was 40% in a total sample of 4736 PCa patients [95% confidence interval (CI): 29-52; P < 0.01; I 2 = 98%]. The results of the subgroup analyses showed the prevalence of CRF after androgen deprivation therapy treatment, radical prostatectomy and radiotherapy to be 42% (95%CI: 20-67, P < 0.01, I 2 = 91%), 21% (95%CI: 16-26, P = 0.87, I 2 = 0%) and 40% (95%CI: 22-58, P < 0.01, I 2 = 90%), respectively. The prevalence of acute and persistent fatigue was 44% (95%CI: 25-64; P < 0.01; I 2 = 93%) and 29% (95%CI: 25-32; P = 0.30; I 2 = 17%), respectively. CONCLUSION: Our meta-analysis showed that fatigue is a common symptom in men with PCa, especially those using hormone therapy.

Helicobacter pylori infection reduces TAMs infiltration in a mouse model of AOM/DSS induced colitis-associated cancer.

Inflammatory bowel disease (IBD) increases the risk of colitis-associated cancer (CAC). Evidences suggest that Helicobacter pylori (H. pylori) infection is associated with a low risk of IBD and protects against experimental colitis in mouse models. However, the effect of H. pylori infection in CAC remains unclear. We previously reported that H. pylori infection increased M2 macrophages in dextran sodium sulfate (DSS)-induced chronic colitis. Tumor-associated macrophages (TAMs) play a pivotal role in colon cancer. Therefore, we established a H. pylori-infected CAC mouse model induced by azoxymethane and DSS to explore the effect of H. pylori infection on TAMs in CAC. Here, we demonstrated that H. pylori infection attenuated the development of CAC by decreasing tumor multiplicity, tumor size, tumor grade and colitis scores. Moreover, H. pylori infection reduced the infiltration of TAMs, particularly M2-like TAMs in CAC tumors, accompanied with the down-regulated pro-inflammatory and pro-tumorigenic factors TNF-α, IL-1ß, IL-6 and IL-23 in tumors of CAC mice. Our study suggests that H. pylori infection can reduce TAMs infiltration and regulate cytokines expression in CAC.

Knockdown of SALL4 inhibits the proliferation and reverses the resistance of MCF-7/ADR cells to doxorubicin hydrochloride.

BACKGROUND: Breast cancer is the most frequent malignancy in women and drug resistance is the major obstacle for its successful chemotherapy. In the present study, we analyzed the involvement of an oncofetal gene, sal-like 4 (SALL4), in the tumor proliferation and drug resistance of human breast cancer. RESULTS: Our study showed that SALL4 was up-regulated in the drug resistant breast cancer cell line, MCF-7/ADR, compared to the other five cell lines. We established the lentiviral system expressing short hairpin RNA to knockdown SALL4 in MCF-7/ADR cells. Down-regulation of SALL4 inhibited the proliferation of MCF-7/ADR cells and induced the G1 phase arrest in cell cycle, accompanied by an obvious reduction of the expression of cyclinD1 and CDK4. Besides, down-regulating SALL4 can re-sensitize MCF-7/ADR to doxorubicin hydrochloride (ADMh) and had potent synergy with ADMh in MCF-7/ADR cells. Depletion of SALL4 led to a decrease in IC50 for ADMh and an inhibitory effect on the ability to form colonies in MCF-7/ADR cells. With SALL4 knockdown, ADMh accumulation rate of MCF-7/ADR cells was increased, while the expression of BCRP and c-myc was significantly decreased. Furthermore, silencing SALL4 also suppressed the growth of the xenograft tumors and reversed their resistance to ADMh in vivo. CONCLUSION: SALL4 knockdown inhibits the growth of the drug resistant breast cancer due to cell cycle arrest and reverses tumor chemo-resistance through down-regulating the membrane transporter, BCPR. Thus, SALL4 has potential as a novel target for the treatment of breast cancer.

[Salvia Miltiorrhiza reduces plasma levels of asymmetric ADMA in patients with non-ST elevation myocardial infarction undergoing percutaneous coronary intervention].

OBJECTIVE: To study changes of plasma ADMA levels of patients with non-ST elevation myocardial infarction (NSTEMI) undergoing percutaneous coronary intervention (PCI) and to explore the effect of Salvia Miltiorrhiza (SM) on them. METHODS: Totally 52 patients with confirmed NSTEMI undergoing PCI were randomly assigned to the SM treated group and the control group, 26 in each group. Patients in the SM treated group received the conventional therapy plus SM (1 g each time, three times per day till one month after PCI). Those in the control group only received the conventional therapy. Plasma ADMA levels were measured before PCI, and at day 1 and 30 after PCI. RESULTS: Plasma ADMA levels in both group obviously decreased at day 30 after PCI with statistical difference (P < 0.01). The decrement was more obviously seen in the SM treated group, with statistical difference when compared with the control group (P < 0.01). CONCLUSIONS: Patients with NSTEMI undergoing PCI could have plasma ADMA levels decreased. Administration of SM just before PCI might be associated with negative regulating plasma ADMA levels.