HOXC6 regulates the antitumor effects of pheophorbide a-based photodynamic therapy in multidrug-resistant oral cancer cells

Abstract

Photodynamic therapy (PDT) has been considered to be a possible candidate approach for the treatment of multidrug-resistant (MDR) cancer. To investigate the photocytotoxicity of pheophorbide a-based PDT on MDR cells, the intracellular pathways were studied using the human oral cancer FaDu cell line and its paclitaxel-selected subline FaDu-PTX. Pheophorbide a (Pa)-PDT induced significant photocytotoxicity in both FaDu and FaDu-PTX cell lines with cell apoptosis greater in FaDu cells compared to FaDu-PTX cells. We found that Hoxc6 and MDR-1 expression was strongly detected in FaDu-PTX cells compared to FaDu cells. Intriguingly, Pa-PDT effectively reduced Hoxc6 and MDR-1 expression in FaDu-PTX cells. The siRNA for HOXC6 can inhibit the intracellular MDR-1 levels in FaDu-PTX cells and induce the phototoxic effects of Pa-PDT. Furthermore, our in vivo studies showed that the Pa-PDT and HOXC6 siRNA significantly reduce the growth of FaDu-PTX xenograft tumors in C3H mice compared with control- and PTX-treated tumors. Histopathology was also used to confirm this antitumor effect. Pa-PDT may be a potential therapeutic modality for multidrug-resistant cancer, and Hoxc6, as a possible contributor to MDR, may reduce the therapeutic potential in multidrug-resistant oral malignancies.

MicroRNA-495 confers inhibitory effects on cancer stem cells in oral squamous cell carcinoma through the HOXC6-mediated TGF-β signaling pathway

“…The overexpression of HOXC5 has also found to be associated with oral carcinogenesis and can significantly boost the development of OSCC [40]. Furthermore, siRNA against HOXC6 significantly reduces the growth of xenograft tumors in mice with oral cancer [31] and upregulation of miR-495 can inhibit the growth of OSCC xenografts in vivo [28], which were in agreement with our in vivo experimental results.…”

“…The blockade of HOXC6-dependent TGF-β signaling pathway is responsible for the suppressed EMT and lymph node metastasis in laryngeal cancer [30]. HOXC6 was found to be abundantly expressed in oral cancer FaDu-PTX cells compared to normal cells [31]. Moreover, the activated TGF-β/Smad signaling pathway is capable to promote the proliferation and suppress the apoptosis of OSCC cells [32].…”

Implications of photodynamic cancer therapy: an overview of PDT mechanisms basically and practically

“…[49], [108], [17], [2], [3], [46], [4], [70], [83] Glioma HPPH: 2-( [51], [92], [37], [89], [84], [36] Sobhani and Samadani J Egypt Natl Canc Inst (2021) 33:34 High-intensity focused ultrasound (HIFU) and radiofrequency ablation (RFA) are mentioned as two competitors of PDT of breast cancer by Banerjee et al HIFU possesses the higher ratio of CD4 + to CD8 + T cell and maybe lower sustained adoptive immune response compare to PDT [9]. In recent years, PDT has remained as an area of interest in palliative treatments and limitation of drug resistance [7].…”