<p>Delicaflavone Reverses Cisplatin Resistance via Endoplasmic Reticulum Stress Signaling Pathway in Non-Small Cell Lung Cancer Cells</p>

Abstract

Background: The incidence and mortality of lung cancer continue to increase around the world; in 2018, new lung cancer cases accounted for 11.6% of all cancer cases, and lung cancer deaths accounted for 18.4% of cancer deaths. Cisplatin (DDP) is a first-line chemotherapy drug for lung cancer; however, DDP resistance can lead to a poor prognosis in patients with lung cancer. Therefore, reversing DDP resistance is a treatment goal. Materials and Methods: Cell counting kit-8 (CCK8) assays, wound healing analyses, Transwell assays, in vitro tumor xenografts, and flow cytometry were used to detect the proliferation, migration, invasion, and apoptosis of multidrug resistant A549/DDP and PC9/ DDP cells, respectively. Western blot was performed to detect protein levels of cleaved caspase-3, CHOP, and GRP78. Results: Delicaflavone inhibited DDP resistance of lung cancer cells and decreased proliferation in a dose-and time-dependent manner. It also decreased migration and invasion and enhanced apoptosis. Western blots showed that delicaflavone overcame DDP resistance by increasing the expression of GRP78 and CHOP and the apoptosis-related protein cleaved caspase-3. Conclusion: Delicaflavone can reverse DDP resistance in A549/DDP and PC9/DDP cells by inhibiting cell proliferation and migration and enhancing apoptosis and cleaved caspase-3 levels by increasing the expression of CHOP and GRP78 protein via the endoplasmic reticular stress pathway. It could be a useful therapeutic adjunct to treat DDP-resistant lung cancer.

Delicaflavone induces apoptosis and autophagy, and improves the cytotoxicity of multiple myeloma cells to cisplatin by inactivating the AKT/mTOR pathway

“…Therefore, induction of autophagy might be helpful for the amelioration of drug resistance in multiple myeloma. Cisplatin resistance in non-small cell lung cancer cells was reversed by delicaflavone [10]. The present study indicated that delicaflavone conferred cisplatin sensitivity in multiple myeloma cells via decreases in both cell viability and proliferation.…”

“…Autophagy also induces multi-drug resistance, leading to cytoprotective effects against anticancer therapy-induced responses [17], suggesting that suppression of autophagy could resensitize cancer cells to anticancer therapies. Because delicaflavone has been shown to resensitize cancer cells by mediating a pathway signaling endoplasmic reticulum stress [10], we then investigated the mechanism underlying delicaflavone-mediated autophagy and drug resistance in multiple myeloma cells.…”

“…For example, Wensong Yao et al [9] found that delicaflavone promoted apoptosis of colorectal cancer cells and repressed colorectal cancer proliferation. Delicaflavone conferred cisplatin sensitivity in non-small cell lung cancer cells [10]. However, the effects of delicaflavone on multiple myeloma cell apoptosis, autophagy, and cisplatin resistance have not yet been reported.…”

Delicaflavone Represses Lung Cancer Growth by Activating Antitumor Immune Response through N6-Methyladenosine Transferases and Oxidative Stress

“…Nude mice or immunocompetent C57BL/6 mice were injected subcutaneously with 5 × 10 4 3LL tumor cells (day 0). On day 4, mice in the DLL group were injected with DLL (0.5 mg/kg/day, s.c.) into the subcutaneous tumors, once a day, for a total of 7 times [ 6 ]. The tumor size was measured every 2 days to monitor tumor growth in mice.…”

“…We previously isolated a new type of biflavonoid compound, delicaflavone (DLL), from Selaginella doederleinii Hieron, and discovered that DLL inhibited A549 cell growth via the Akt/mTOR/p70S6K signaling pathway [ 5 ]. DLL reduced cisplatin resistance in lung cancer by modulating endoplasmic reticulum stress signaling [ 6 ]; however, it is unknown whether DLL can activate an antitumor immune response.…”