Biochimica et biophysica acta. General subjects · 2026
Quercetin, an active component of Qiu's HuaShi decoction, suppresses glycolysis in cervical epithelial cells to reduce HPV infection via modulating the PRKACA/cAMP/PKA/CREB pathway.
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Xia Mengting, Xu Haiou, Ding Nan, Wang Xinyan
Аннотация
BACKGROUND: Cervical cancer is strongly associated with persistent infection with high-risk human papillomavirus (HPV) and poses a substantial threat to women's health. Qiu's HuaShi Decoction (QHD) exhibits potential in cervical cancer treatment, yet its underlying mechanism remains unclear.
METHODS: Network pharmacology was utilized to screen the core targets of QHD against HPV-associated cervical cancer. The anti-tumor effects of quercetin were evaluated through integrated in vivo and in vitro experiments. Immunofluorescence staining was applied to observe the status of HPV16 infection. Meanwhile, qRT-PCR and western blot were used to detect the mRNA and protein expression levels of HPV16 oncogenes E6 and E7. Immunohistochemistry (IHC) was used for in situ validation of protein expression in animal tissues. In addition, western blot was performed to quantify the protein levels of key molecules involved in the PRKACA/PKA/CREB axis and core glycolytic regulators. Furthermore, cAMP content, cellular glucose uptake, lactate production and extracellular acidification rate (ECAR) and oxygen consumption rate (OCR) were assessed by commercial kits. Additionally, PRKACA overexpression experiments were performed to dissect the regulatory role of PRKACA in quercetin-mediated effects.
RESULTS: Network pharmacology analysis identified quercetin and PRKACA as the core targets of QHD for combating HPV-associated cervical cancer. Quercetin inhibited early HPV16 infection, downregulated HPV16 E6/E7 expression, and suppressed cell proliferation. Mechanistically, quercetin reduced intracellular cAMP levels, inactivated the cAMP/PKA/CREB signaling axis, and suppressed the expression of key glycolytic proteins. Consistently, quercetin suppressed glycolytic phenotypes, including reduced glucose uptake, lactate secretion, and ATP production, accompanied by decreased ECAR and restored OCR in cervical epithelial cells. These phenotypic effects were reversed by PRKACA overexpression.
CONCLUSIONS: Quercetin exerts its anti-tumor effects against HPV-related cervical cancer by inhibiting PRKACA expression to disrupt cAMP/PKA/CREB/glycolysis signaling axis, providing a molecular basis for the clinical application of QHD.
METHODS: Network pharmacology was utilized to screen the core targets of QHD against HPV-associated cervical cancer. The anti-tumor effects of quercetin were evaluated through integrated in vivo and in vitro experiments. Immunofluorescence staining was applied to observe the status of HPV16 infection. Meanwhile, qRT-PCR and western blot were used to detect the mRNA and protein expression levels of HPV16 oncogenes E6 and E7. Immunohistochemistry (IHC) was used for in situ validation of protein expression in animal tissues. In addition, western blot was performed to quantify the protein levels of key molecules involved in the PRKACA/PKA/CREB axis and core glycolytic regulators. Furthermore, cAMP content, cellular glucose uptake, lactate production and extracellular acidification rate (ECAR) and oxygen consumption rate (OCR) were assessed by commercial kits. Additionally, PRKACA overexpression experiments were performed to dissect the regulatory role of PRKACA in quercetin-mediated effects.
RESULTS: Network pharmacology analysis identified quercetin and PRKACA as the core targets of QHD for combating HPV-associated cervical cancer. Quercetin inhibited early HPV16 infection, downregulated HPV16 E6/E7 expression, and suppressed cell proliferation. Mechanistically, quercetin reduced intracellular cAMP levels, inactivated the cAMP/PKA/CREB signaling axis, and suppressed the expression of key glycolytic proteins. Consistently, quercetin suppressed glycolytic phenotypes, including reduced glucose uptake, lactate secretion, and ATP production, accompanied by decreased ECAR and restored OCR in cervical epithelial cells. These phenotypic effects were reversed by PRKACA overexpression.
CONCLUSIONS: Quercetin exerts its anti-tumor effects against HPV-related cervical cancer by inhibiting PRKACA expression to disrupt cAMP/PKA/CREB/glycolysis signaling axis, providing a molecular basis for the clinical application of QHD.