Background/Aims: Although photodynamic therapy (PDT) can relieve esophageal obstruction and prolong survival time of patients with esophageal cancer, it can induce nuclear factor-kappa B (NF-κB) activation in many cancers, which plays a negative role in PDT. Dihydroartemisinin (DHA), the most potent artemisinin derivative, can enhance the effect of PDT on esophageal cancer cells. However, the mechanism is still unclear. Methods: We generated stable cell lines expressing the super-repressor form of the NF-κB inhibitor IκBα and cell lines with lentivirus vector-mediated silencing of the HIF-1α gene. Esophageal xenograft tumors were created by subcutaneous injection of Eca109 cells into BALB/c nude mice. Four treatment groups were analyzed: a control group, photosensitizer alone group, light alone group, and PDT group. NF-κB expression was detected by an electrophoretic mobility shift assay, hypoxia-inducible factor α (HIF-1α) and vascular endothelial growth factor (VEGF) by real-time PCR, NF-κB, HIF-1α, and VEGF protein by western blot, and Ki-67, HIF-1α, VEGF, and NF-κB protein by immunohistochemistry. Results: PDT increased NF-κB activity and the gene expression of HIF-1α and VEGF in vitro and in vivo. In contrast, the DHA groups, particularly the combined DHA and PDT treatment group, abolished the effect. The combined treatment significantly inhibited tumor growth in vitro and in vivo. NF-κB activity and HIF-1α expression were also reduced in the stable IκBα expression group, whereas the former showed no change in HIF-1α-silenced cells. Conclusion: DHA might increase the sensitivity of esophageal cancer cells to PDT by inhibiting the NF-κB/HIF-1α/VEGF pathway.
Despite recent advances in chemotherapy and surgical resection, the 5-year survival rate of esophageal cancer still remains at the low level. Therefore, it is very important to discover a new agent to improve the life expectancy of patients with esophageal cancer. Dihydroartemisinin (DHA), a semisynthetic derivative of artemisinin, has recently exhibited promising anticancer activity against various cancer cells. But so far, the specific mechanism remains unclear. We have previously demonstrated that DHA reduced viability of esophageal cancer cells in a dose-dependent manner in vitro and induced cell cycle arrest and apoptosis. Here, we extended our study to further observe the efficacy of DHA on esophageal cancer cells in vivo. In the present study, for the first time, we found that DHA significantly inhibits cell proliferation in xenografted tumor compared with the control. The mechanism was that DHA induced cell apoptosis in both human esophageal cancer cell lines Eca109 and Ec9706 in vivo in a dose-dependent manner. The results suggested that DHA was a promising agent against esophageal cancer in the clinical treatment.
e18050 Background: Targeted therapy and immunotherapy are efficacious treatment options for advanced head and neck cancer. However, the treatment of locally advanced hypopharyngeal carcinoma still consists of surgery, radiotherapy, and chemotherapy. Combining docetaxel, cisplatin (DDP), and 5-fluorouracil as standard induction chemotherapy provided opportunities for further surgical larynx preservation in some patients. This study retrospectively analyzed the short-term efficacy and adverse events of nab-paclitaxel + DDP/nedaplatin (NDP) + S-1 as an induction chemotherapy regimen for locally advanced hypopharyngeal cancer. Methods: The study included 22 patients with locally advanced hypopharyngeal cancer treated via induction chemotherapy at the Affiliated Hospital of Guilin Medical University from December 2020 to July 2022. Among these patients, 11 received nab-paclitaxel (125mg/m2, days 1 and 8) + DDP (35- 40mg/m2, days 1-2) or NDP (65-75mg/m2, day 1) + S-1 (30-40 mg/m2 bid, days 1-14) every 21 days for a total of three cycles. A baseline enhanced magnetic resonance imaging (MRI) of the head and neck was performed for all patients to confirm the presence of suspicious lesions. Another MRI was performed before the third cycle of induction chemotherapy to confirm the efficacy of the treatment regimen. Patients, who were responsive to the induction therapy, were allowed to choose their respective sequential therapy regimen. The response was assessed using RECIST v1.1. Adverse reactions were evaluated according to CTCAE5.0. Results: The response to treatment of the 11 patients was assessed by the investigators. There was one patient with a complete response (9.1%), eight patients with a partial response (72.7%), and two patients with stable disease (18.2%). The objective response rate was 81.8% (9/11), and the disease control rate was 100%. Five of the nine patients with a partial or complete response opted for surgery after three cycles of induction chemotherapy. The pathological complete response rate was 100% (5/5). The most common grade 3 treatment-emergent adverse events (TEAE) were leukopenia (45.5%), neurotoxicity (36.3%), and anemia (18.2%). Grade 4/5 TEAEs were not observed. Conclusions: Based on the results of this retrospective study, the nab-paclitaxel + DDP/ NDP + S-1 was a safe and viable induction chemotherapy regimen for locally advanced hypopharyngeal cancer. It allowed more options for subsequent treatment. Further research is warranted to validate the findings of this study. [Table: see text]
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