ABSTRACT
BACKGROUND: Breast cancer is a serious threat to women's health with high morbidity and mortality. The development of more effective therapies for the treatment of breast cancer is strongly warranted. Growing evidence suggests that targeting glucose metabolism may be a promising cancer treatment strategy. We previously identified a new glyceraldehyde-3-phosphate dehydrogenase (GAPDH) inhibitor, DC-5163, which shows great potential in inhibiting tumor growth. Here, we evaluated the anticancer potential of DC-5163 in breast cancer cells. METHODS: The effects of DC-5163 on breast cancer cells were investigated in vitro and in vivo. Seahorse, glucose uptake, lactate production, and cellular ATP content assays were performed to examine the impact of DC-5163 on cellular glycolysis. Cell viability, colony-forming ability, cell cycle, and apoptosis were assessed by CCK8 assay, colony formation assay, flow cytometry, and immunoblotting respectively. The anticancer activity of DC-5163 in vivo was evaluated in a mouse breast cancer xenograft model. RESULTS: DC-5163 suppressed aerobic glycolysis and reduced energy supply of breast cancer cells, thereby inhibiting breast cancer cell growth, inducing cell cycle arrest in the G0/G1 phase, and increasing apoptosis. The therapeutic efficacy was assessed using a breast cancer xenograft mouse model. DC-5163 treatment markedly suppressed tumor growth in vivo without inducing evident systemic toxicity. Micro-PET/CT scans revealed a notable reduction in tumor 18F-FDG and 18F-FLT uptake in the DC-5163 treatment group compared to the DMSO control group. CONCLUSIONS: Our results suggest that DC-5163 is a promising GAPDH inhibitor for suppressing breast cancer growth without obvious side effects. 18F-FDG and 18F-FLT PET/CT can noninvasively assess the levels of glycolysis and proliferation in tumors following treatment with DC-5163.
ABSTRACT
This study investigated the relationship among the severity of hearing impairment,vestibular function and balance function in patients with idiopathic sudden sensorineural hearing loss (ISSNHL).A total of 35 ISSNHL patients (including 21 patients with vertigo) were enrolled.All of the patients underwent audiometry,sensory organization test (SOT),caloric test,cervical vestibular-evoked myogenic potential (cVEMP) test and ocular vestibular-evoked myogenic potential (oVEMP) test.Significant relationship was found between vertigo and hearing loss grade (P=0.009),and between SOT VEST grade and hearing loss grade (P=0.001).The abnormal rate of oVEMP test was the highest,followed by the abnormal rates of caloric and cVEMP tests,not only in patients with vertigo but also in those without vertigo.The vestibular end organs were more susceptible to damage in patients with vertigo (compared with patients without vertigo).Significant relationship was found between presence of vertigo and SOT VEST grade (P=0.010).We demonstrated that vestibular end organs may be impaired not only in patients with vertigo but also in patients without vertigo.The cochlear and vestibular impairment could be more serious in patients with vertigo than in those without vertigo.Vertigo does not necessarily bear a causal relationship with the impairment of the vestibular end organs.SOT VEST grade could be used to reflect the presence of vertigo state in the ISSNHL patients.Apart from audiometry,the function of peripheral vestibular end organs and balance function should be evaluated to comprehensively understand ISSNHL.Better assessment of the condition will help us in clinical diagnosis,treatment and prognosis evaluation of ISSNHL.