Abstract
Since a portion of patients with nasopharyngeal carcinoma (NPC) do not benefit much from current standard treatments, it is still needed to discover new therapeutic drugs to improve the prognosis of the patients. Considering that Chinese traditional medicine plays a role in inhibiting tumor progression, in this study, we aimed to investigate whether a Chinese herbal formula, Qing Yan Li Ge Tang (QYLGT), has the anticancer activity in NPC cells and explore the underlying mechanism as well. MTT assay, colony formation assay, immunoblotting assay, and DNA laddering assay were performed to assess cell viability, cell colony formation, protein expression, and DNA fragmentation, respectively. Results show that QYLGT was able to inhibit the cell viability and decrease colony formation ability in NPC cells. QYLGT could also increase the formation of intracellular vacuoles and induce the autophagy-related protein expressions, including Atg3, Atg6, and Atg12-Atg5 conjugate in NPC cells. Treatment with an autophagy inhibitor, 3-methyladenine, could significantly recover QYLGT-inhibited cell viability of NPC cells. In addition, QYLGT did not significantly induce apoptosis in NPC cells. We also found that QYLGT had the ability to activate phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of the rapamycin (mTOR) pathway. Treatment with PI3K inhibitors, LY294002 and wortmannin, or mTOR inhibitors, rapamycin and Torin 1, could not only recover QYLGT-inhibited cell viability of NPC cells but also inhibit Atg3 expression. Taken together, our results demonstrated that QYLGT could induce autophagic cell death in NPC cells through the PI3K/Akt/mTOR pathway.
Highlights
Nasopharyngeal carcinoma (NPC) is a malignant tumor with high metastatic features originating from the nasopharynx. e incidence rate of NPC is generally low around the world [1].in some distinct areas in Southern China, such as Guangdong and Hong Kong, the incidence rate is rather high about 20–30 per 100,000 persons per year [2]
HONE-1 and NPC-TW01 NPC cells were treated with different doses of Qing Yan Li Ge Tang (QYLGT) (20–100 μg/ml to HONE-1 cells and 0.1–2.5 mg/ml to NPC-TW01 cells, respectively), and cell viabilities were measured by MTT assay
We used IC50 of QYLGT as a standard concentration to further study the time-course effect on NPC cells, which were treated with IC50 of QYLGT for 0, 24, 48, and 72 h, respectively
Summary
Nasopharyngeal carcinoma (NPC) is a malignant tumor with high metastatic features originating from the nasopharynx. e incidence rate of NPC is generally low (under 1 per 100,000 persons per year) around the world [1].in some distinct areas in Southern China, such as Guangdong and Hong Kong, the incidence rate is rather high about 20–30 per 100,000 persons per year [2]. E incidence rate of NPC is generally low (under 1 per 100,000 persons per year) around the world [1]. Evidence-Based Complementary and Alternative Medicine rate of about 85–90% [3,4,5], a small portion of NPC patients have no beneficial effects from the treatments. Several studies have shown that Chinese herbal medicine plays an important role in the prevention and treatment of cancer. The Chinese herbal formulas, such as Zeng-Sheng-Ping and Yangyinjiedu, have been shown to inhibit tumor progression in animal models [6, 7]. Qing Yan Li Ge Tang (QYLGT), a Chinese herbal formula, is widely used in clinical applications to the patients with acute upper respiratory infection, allergic rhinitis, cough, or chronic pharyngitis; it is still unknown whether it has antitumor effects
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