Acupuncture is widely recognized as an effective therapy for premature ovarian failure (POF) in clinical, but information about its potential mechanisms is rarely explored. To investigate the mechanism, fifty SD female rats were randomly divided into normal group, POF group, POF+estradiol-valerate group (abbreviated as estradiol group), and POF+acupuncture group (abbreviated as acupuncture group). The estrous cycle of the rats was tracked by vaginal smears. Their ovaries morphology was observed by hematoxylin-eosin staining. The apoptotic level of granulosa cells was detected by in situ TUNEL fluorescence staining assay. Serum follicle-stimulating hormone (FSH) and estrogen (E2) levels were measured by enzyme-linked-immunosorbent-assay (ELISA). Protein and gene expression of PI3K, Akt, bcl-2, and bax were detected by Western blotting and qPCR. In the acupuncture and estradiol groups, compared with the POF group as controls, the apoptosis number of granulosa cells was significantly decreased (p < 0.05). FSH levels were decreased, while E2 levels were increased (p > 0.05). The gene and protein expression levels of PI3K, Akt, and bcl-2 were increased, while the expression levels of bax were decreased (p < 0.05), and the protein expression level of p-Akt increased. There was no significant difference between the acupuncture group and the estradiol group (p > 0.05). Acupuncture was able to regulate hormone levels in POF rats, up-regulate PI3K/Akt signaling pathway, and reduce the apoptosis of granulosa cells. This may be one of the mechanisms of acupuncture treating premature ovarian failure.
Colon
cancer is an aggressive malignancy with very limited therapeutic
approaches. The available therapeutic agents for colon cancer show
strong adverse effects and poor effectiveness, indicating the urgent
need to identify new therapeutic drugs for this malignancy. Kaempferol,
a flavonoid found in a variety of natural foods, exhibits significant
inhibitory effects on colon cancer. Here, it was found that kaempferol
inhibited the proliferation of human colon cancer cells HCT116 and
DLD1 in a dose-dependent manner, and the IC50 values were
63.0 ± 12.9 and 98.3 ± 15.9 μM, respectively. Also,
kaempferol treatment delayed G1 phase progression of cell cycle and
induced apoptosis. Aerobic glycolysis is the major energy source for
various tumor growths, including colon cancer. Indeed, kaempferol
treatment impaired glucose consumption, which subsequently led to
reduced lactic acid accumulation and ATP production. Mechanistically,
kaempferol promoted the expression of miR-339-5p. Further studies
identified hnRNPA1 and PTBP1 as two direct targets of miR-339-5p.
By directly targeting hnRNPA1 and PTBP1, miR-339-5p reduced the expression
of M2-type pyruvate kinase (PKM2) but induced that of PKM1. In conclusion,
these data demonstrate that by modulating miR-339-5p-hnRNPA1/PTBP1-PKM2
axis, kaempferol inhibits glycolysis and colon cancer growth, which
reveals a new explanation for the molecular mechanism underlying kaempferol
anti-tumor.
Resistance to 5-Fluorouracil (5-Fu) chemotherapy is the main cause of treatment failure in the cure of colon cancer. Therefore, there is an urgent need to explore a safe and effective multidrug resistance reversal agent for colorectal cancer, which would be of great significance for improving clinical efficacy. The dietary flavonoid kaempferol plays a key role in the progression of colorectal cancer and 5-Fu resistance. However, the molecular mechanism of kaempferol in reversing 5-Fu resistance in human colorectal cancer cells is still unclear. We found that kaempferol could reverse the drug resistance of HCT8-R cells to 5-Fu, suggesting that kaempferol alone or in combination with 5-Fu has the potential to treat colorectal cancer. It is well known that aerobic glycolysis is related to tumor growth and chemotherapy resistance. Indeed, kaempferol treatment significantly reduced glucose uptake and lactic acid production in drug-resistant colorectal cancer cells. In terms of mechanism, kaempferol promotes the expression of microRNA-326 (miR-326) in colon cancer cells, and miR-326 could inhibit the process of glycolysis by directly targeting pyruvate kinase M2 isoform (PKM2) 3′-UTR (untranslated region) to inhibit the expression of PKM2 or indirectly block the alternative splicing factors of PKM mRNA, and then reverse the resistance of colorectal cancer cells to 5-Fu. Taken together, our data suggest that kaempferol may play an important role in overcoming resistance to 5-Fu therapy by regulating the miR-326-hnRNPA1/A2/PTBP1-PKM2 axis.
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