Network pharmacology, molecular docking and experimental study of CEP in nasopharyngeal carcinoma.

ETHNOPHARMACOLOGICAL RELEVANCE: The Stephania cephalantha Hayata is an important traditional medicinal plant widely used in traditional medicine to treat cancer. Cepharanthine (CEP) was extracted from the roots of Stephania cephalantha Hayata. It has been found to exhibit anticancer activity in different types of cancer cells. Nevertheless, the activity of CEP against nasopharyngeal carcinoma (NPC) and its underlying mechanism warrant further investigation. AIMS OF THE STUDY: NPC is an invasive and highly metastatic malignancy that affects the head and neck region. This research aimed to investigate the pharmacological properties and underlying mechanism of CEP against NPC, aiming to offer novel perspectives on treating NPC using CEP. MATERIALS AND METHODS: In vitro, the pharmacological activity of CEP against NPC was evaluated using the CCK-8 assay. To predict and elucidate the anticancer mechanism of CEP against NPC, we employed network pharmacology, conducted molecular docking analysis, and performed Western blot experiments. In vivo validation was performed through a nude mice xenograft model of human NPC, Western blot and immunohistochemical (IHC) assays to confirm pharmacological activity and the mechanism. RESULTS: In a dose-dependent manner, the proliferation and clonogenic capacity of NPC cells were significantly inhibited by CEP. Additionally, NPC cell migration was suppressed by CEP. The results obtained from network pharmacology experiments revealed that anti-NPC effect of CEP was associated with 8 core targets, including EGFR, AKT1, PIK3CA, and mTOR. By performing molecular docking, the binding capacity of CEP to the candidate core proteins (EGFR, AKT1, PIK3CA, and mTOR) was predicted, resulting in docking energies of -10.0 kcal/mol for EGFR, -12.4 kcal/mol for PIK3CA, -10.8 kcal/mol for AKT1, and -8.6 kcal/mol for mTOR. The Western blot analysis showed that CEP effectively suppressed the expression of EGFR and the phosphorylation levels of downstream signaling proteins, including PI3K, AKT, mTOR, and ERK. After CEP intervention, a noteworthy decrease in tumor size, without inducing any toxicity, was observed in NPC xenograft nude mice undergoing in vivo treatment. Additionally, IHC analysis demonstrated a significant reduction in the expression levels of EGFR and Ki-67 following CEP treatment. CONCLUSION: CEP exhibits significant pharmacological effects on NPC, and its mechanistic action involves restraining the activation of the EGFR/PI3K/AKT pathway. CEP represents a promising pharmaceutical agent for addressing and mitigating NPC.

The need for psychological counseling in breast cancer patients before radiotherapy during the COVID-19 pandemic.

The aims of this study were to explore the need for psychological counseling in breast cancer patients before radiotherapy during the COVID-19 pandemic, to distinguish which type of psychological guidance they demanded and to investigate the related factors that could be associated with the need for psychological counseling. A total of 112 eligible patients diagnosed with stage I-IV breast cancer who had received surgery were included. The self-rating depression scale (SDS), self-rating anxiety scale (SAS), Pittsburgh sleep quality index (PSQI), cancer fatigue scale (CFS), and survey for the need for psychological counseling were completed for all subjects prior to radiotherapy. A total of 8.9% and 3.6% of patients suffered from depression and anxiety during the COVID-19 pandemic, respectively. The prevalence of sleep disturbance was 62.5%. Only 12.5% of the patients needed psychological counseling, especially for the type of tumor diagnosis and treatment rather than COVID-19-related protection. The higher the total CFS score was, the lower the need for psychological counseling in breast cancer patients during this pandemic (OR = 0.91, 95% CI = 0.84-0.98). Patients who received 7-8 chemotherapeutic cycles had 6.7 times the risk of needing psychological counseling when compared with those who received 1-6 chemotherapeutic cycles. Fewer breast cancer patients suffered from depression and anxiety before radiotherapy during the COVID-19 pandemic. However, a large number of patients complained of sleep disturbance and fatigue. The majority of patients did not need psychological counseling. More chemotherapeutic cycles or less fatigue could increase their risk of needing psychological counseling, especially for tumor diagnosis and treatment, but not COVID-19-related protection.