scholarly journals Inhibitory Effects of HangAmDan-B1 (HAD-B1) Combined With Afatinib on H1975 Lung Cancer Cell–Bearing Mice

2019 ◽  
Vol 18 ◽  
pp. 153473541983076 ◽  
Author(s):  
Hwa Jeong Kang ◽  
Jeehye Kim ◽  
Seong Hyeok Cho ◽  
So-Jung Park ◽  
Hwa-Seung Yoo ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Cycle ◽  
Cancer Cells ◽  
Combined Treatment ◽  
Lung Cancer Cells ◽  
Control Group ◽  
Dependent Manner ◽  
Antibody Microarray ◽  
Double Mutation

Epidermal growth factor receptor mutation-positive non–small cell lung cancer is cared for mainly by target therapeutics in the clinical treatment at present. We investigated the antitumor effect of HangAmDan-B1 (HAD-B1) combined with afatinib on H1975 (L858R/T790M double mutation) lung cancer cells. The combined treatment of HAD-B1 with afatinib inhibited the proliferation of H1975 cells in a dose-dependent manner compared with the treatment of afatinib or HAD-B1 alone. The combined treatment group significantly induced early apoptosis and cell cycle arrest of the cells compared with afatinib- or HAD-B1-treated control group. Profile analysis of cell cycle proteins in H1975 cells treated with the combination of HAD-B1 and afatinib using InnoPharmaScreen antibody microarray showed downregulation of pERK1/2 and upregulation of p16 in the cells. In vivo tumor growth assay in xenograft animal model of human H1975 lung cancer cells revealed that the mean tumor volume in the group treated with the combination of HAD-B1 and afatinib showed a significant reduction compared with the control groups.

Synergy of nanodiamond-doxorubicin conjugates and PD-L1 blockade effectively turns tumor associated macrophages against tumor cells

2021 ◽  
Author(s):  
Huazhen Xu ◽  
Tongfei Li ◽  
Chao Wang ◽  
Yan Ma ◽  
Yan Liu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Tumor Cell ◽  
Cancer Cells ◽  
Tumor Cells ◽  
Lung Cancer Cells ◽  
Dependent Manner ◽  
Tumor Associated Macrophages ◽  
M1 Type

Abstract Background: Tumor-associated macrophages (TAM) are the most abundant stromal cells in the tumor microenvironment. Turning the TAM against their host tumor cells is an intriguing therapeutic strategy particularly attractive for patients with immunologically “cold” tumors. This concept was mechanistically demonstrated on in vitro human and murine lung cancer cells and their corresponding TAM models through combinatorial use of nanodiamond-doxorubicin conjugates (Nano-DOX) and a PD-L1 blocking agent BMS-1. Nano-DOX are an agent previously proved to be able to stimulate tumor cells’ immunogenicity and thereby reactivate the TAM into the anti-tumor M1 phenotype. Results: Nano-DOX were first shown to stimulate the tumor cells and the TAM to release the cytokine HMGB1 which, regardless of its source, acted through the RAGE/NF-κB pathway to induce PD-L1 in the tumor cells and PD-L1/PD-1 in the TAM. Interestingly, Nano-DOX also induced NF-κB-dependent RAGE expression in the tumor cells and thus reinforced HMGB1’s action thereon. Then, BMS-1 was shown to enhance Nano-DOX-stimulated M1-type activation of TAM both by blocking Nano-DOX-induced PD-L1 in the TAM and by blocking tumor cell PD-L1 ligation with TAM PD-1. The TAM with enhanced M1-type repolarization both killed the tumor cells and suppressed their growth. BMS-1 could also potentiate Nano-DOX’s action to suppress tumor cell growth via blocking of Nano-DOX-induced PD-L1 therein. Finally, Nano-DOX and BMS-1 achieved synergistic therapeutic efficacy against in vivo tumor grafts in a TAM-dependent manner. Conclusions: PD-L1/PD-1 upregulation mediated by autocrine and paracrine activation of the HMGB1/RAGE/NF-κB signaling is a key response of lung cancer cells and their TAM to stress, which can be induced by Nano-DOX. Blockade of Nano-DOX-induced PD-L1, both in the cancer cells and the TAM, achieves enhanced activation of TAM-mediated anti-tumor response.

scholarly journals Furanodiene Induces Endoplasmic Reticulum Stress and Presents Antiproliferative Activities in Lung Cancer Cells

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Wen-Shan Xu ◽  
Yuan-Ye Dang ◽  
Jia-Jie Guo ◽  
Guo-Sheng Wu ◽  
Jin-Jian Lu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Endoplasmic Reticulum ◽  
Er Stress ◽  
Cancer Cells ◽  
Combined Treatment ◽  
Lung Cancer Cells ◽  
Chinese Medicinal Herb ◽  
Homologous Protein ◽  
D Cells

Furanodiene (FUR) is a natural terpenoid isolated fromCurcumae Rhizoma, a well-known Chinese medicinal herb that presents antiproliferation activities in several cancer cell lines. In this study, we demonstrated that FUR concentration dependently inhibits the cell proliferation of A549, NIH-H1299, and 95-D lung cancer cells.β-elemene, another terpenoid isolated fromCurcumae Rhizoma, exhibited weaker antiproliferative effects in A549 and NIH-H1299 cells and activities similar to FUR in 95-D cells. FUR significantly inhibited colony formation in A549 and 95-D cells and upregulated both the mRNA and protein expression levels of binding immunoglobulin protein (BIP) and C/EBP homologous protein (CHOP), indicating that endoplasmic reticulum (ER) stress is induced. FUR treatment led to the accumulation of CHOP in the nucleus, which further confirms induction of ER stress. Furthermore, combined treatment of FUR with paclitaxel showed significant synergetic activities in NIH-H1299 and 95-D cells, suggesting its potential roles in combination therapy. These findings provide a basis for the further study of the anticancer effectsin vivoand the internal mechanisms of FUR.

scholarly journals Capilliposide Isolated fromLysimachia capillipesHemsl. Induces ROS Generation, Cell Cycle Arrest, and Apoptosis in Human Nonsmall Cell Lung Cancer Cell Lines

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Zheng-hua Fei ◽  
Kan Wu ◽  
Yun-liang Chen ◽  
Bing Wang ◽  
Shi-rong Zhang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Nonsmall Cell Lung Cancer ◽  
Control Group ◽  
Ros Generation ◽  
Dependent Manner ◽  
Apoptotic Pathway ◽  
Cycle Arrest

Several data has reported that capilliposide, extracted from a traditional Chinese medicine,Lysimachia capillipesHemsl. (LC) could exhibit inhibitory effect on cell proliferation in various cancers. The current study investigated the antitumor efficacy ofCapilliposideand elucidated its potential molecular mechanism involved in vivo and vitro. Our results indicated that LC capilliposide inhibited proliferation of lung cancer cells in a dose-dependent manner. LC capilliposide induced cell cycle arrest at the S stage and enhanced apoptosis in NSCLC cells. Treatment with LC capilliposide increased the intracellular level of ROS, which activated the mitochondrial apoptotic pathway. Blockage of ROS by NAC highly reversed the effect of LC capilliposide on apoptosis. Xenograft tumor growth was significantly lower in the LC-treated group compared with the untreated control group(P<0.05). The results also show that LC treatment does not produce any overt signs of acute toxicity in vivo. These findings demonstrate that LC capilliposide could exert an anti-tumor effect on NSCLC through mitochondrial-mediated apoptotic pathway and the activation of ROS is involved.

scholarly journals Effects of Apatinib on the “Stemness” of Non-Small-Cell Lung Cancer Cells In Vivo and Its Related Mechanisms

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Bin Yang ◽  
Yan Wang ◽  
Zhuoying Chen ◽  
Yi-Ming Feng ◽  
Liang-Liang Shi
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cancer Cells ◽  
Signaling Pathways ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Lung Cancer Cells ◽  
Control Group ◽  
Small Cell Lung

Objective. To investigate the effects of Apatinib on the “stemness” of lung cancer cells in vivo and to explore its related mechanisms. Methods. A xenograft model of lung cancer cells A549 was established in nude mice and randomized into a control group (n = 4) and an Apatinib group (n = 4). Tumor tissues were harvested after 2 weeks, and mRNA was extracted to detect changes in stemness-related genes (CD133, EPCAM, CD13, CD90, ALDH1, CD44, CD45, SOX2, NANOG, and OCT4) and Wnt/β-catenin, Hedgehog, and Hippo signal pathways. Results. Compared with the control group, the volume and weight of nude mice treated with Apatinib were different and had statistical significance. Apatinib inhibited the expressions of ABCG2, CD24, ICAM-1, OCT4, and SOX2 and upregulated the expressions of CD44, CD13, and FOXD3. Apatinib treatment also inhibited the Wnt/β-catenin, Hedgehog, and Hippo signaling pathways. Conclusion. Apatinib suppressed the growth of non-small-cell lung cancer cells by repressing the stemness of lung cancer through the inhibition of the Hedgehog, Hippo, and Wnt signaling pathways.

Extracts from the Roots of Lindera strychifolia Induces Apoptosis in Lung Cancer Cells and Prolongs Survival of Tumor-bearing Mice

2003 ◽  
Vol 31 (06) ◽  
pp. 857-869 ◽  
Author(s):  
Yun-Mo Li ◽  
Yasushi Ohno ◽  
Shinya Minatoguchi ◽  
Kazunori Fukuda ◽  
Tetsuro Ikoma ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Oral Administration ◽  
Tumor Cell ◽  
Cancer Cells ◽  
Human Lung ◽  
Lung Cancer Cells ◽  
Human Lung Cancer ◽  
Dependent Manner ◽  
Dose Dependent

Lindera strychifolia, a scandent shrub Lauraceous medicinal plant, has been used in Chinese traditional medicine as a palliative and an anti-spasmodic. It also shows cytotoxic effects against several tumor cell lines and inhibits marcromolecule biosynthesis. This study investigated the anti-tumor effects of L. strychifolia extract against lung cancer cells using in vitro and in vivo models. Two human lung cancer cell lines A549 (adenocarcinoma) and SBC-3 (small cell carcinoma), and a non-tumor cell line 3T3-L1 (mice fibroblasts) were subjected to L. strychifolia extract treatment. On lung cancer cells, L. strychifolia induced cell growth inhibition in a dose-dependent manner. Conversely, the extract did not show any significant cytotoxic effect on 3T3-L1 cells. Therefore, the extract is specific for tumor cells. Tumor cells treated with L. strychifolia extract showed typical morphological appearance of apoptosis including nuclei fragmentation and cell condensation. The in vivo effects of L. strychifolia extract were investigated in C57BL/6 mice transplanted with Lewis lung cancer (LL-2) cells, and in BALB/c nude mice transplanted with A549 or SBC-3 human lung cancer cells. Oral administration of L. strychifolia extract prolonged survival time and inhibited tumor growth in a dose-dependent manner by inducing apoptosis in the LL-2 cell mice model. Furthermore, in A549 or SBC-3 cell nude mice models, oral administration of L. strychifolia extract also significantly inhibited tumor growth at the 5.0 mg/ml concentration. These findings suggested that the components of L. strychifolia have anticancer activity and may contribute to clinical applications in the prevention and treatment of lung cancer.

MicroRNA-1254 Suppresses Epithelial-Mesenchymal Transition by Upregulating c-Cellular Myelocytomatosis Oncogene (c-Myc) and Alleviates Drug Resistance in Lung Cancer

2021 ◽  
Vol 11 (11) ◽  
pp. 2146-2152
Author(s):  
Liu Shi ◽  
Yu Xiong ◽  
Xiaoyan Hu
Keyword(s):  
Lung Cancer ◽  
Drug Resistance ◽  
Cancer Cells ◽  
Epithelial Mesenchymal Transition ◽  
Combined Treatment ◽  
Lung Cancer Cells ◽  
Drug Resistant ◽  
Mesenchymal Transition ◽  
Huge Challenge

Drug resistance is a huge challenge during the management of diseases. MicroRNA (miRNA) dys-regulation is known to contribute to tumor progression. Herein we aimed to explore miR-1254’s role in drug resistance in lung cancer. In the present study, we used Pabolizumab to treat drug-resistant and non-drug resistant lung cancer cells followed by analysis of miR-1254 expression by RT-qPCR, epithelial-mesenchymal transition (EMT) related protein and c-Myc expression by western blot, E-cadherin and N-cadherin level by immunofluorescence. Additionally, mouse model of lung cancer was treated with miR-1254 mimic and/or Pabolizumab to assess miR-1254’s role in lung cancer in vivo. Drug-resistant lung cancer cells exhibited significantly increased viability upon treatment with Pabolizumab with decreased miR-1254 expression. Besides, Pabolizumab upregulated E-caderin and downregulated N-cadherin. Importantly, miR-1254 bound to c-Myc in cancer cells. In the presence of miR-1254 mimic or siRNA (si)-c-Myc, the chemosensitivity of lung cancer cells was increased whereas miR-1254 inhibitor augmented cell resistance to Pabolizumab. Furthermore, the chemosensitivity induced by c-Myc could be depleted by miR-1254 inhibitor. Combined treatment of miR-1254 mimic and Pabolizumab significantly decreased tumor weight and volume, and reduced c-Myc level. In conclusion, miR-1254 might suppress EMT by inhibiting c-Myc expression in lung cancer and decrease drug resistance.

scholarly journals Biochanin A Induces S Phase Arrest and Apoptosis in Lung Cancer Cells

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Yan Li ◽  
Haiyang Yu ◽  
Fengfeng Han ◽  
Mengmeng Wang ◽  
Yong Luo ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Cycle ◽  
Cancer Cells ◽  
Caspase 3 ◽  
Lung Cancer Cells ◽  
Biochanin A ◽  
Dependent Manner ◽  
Cycle Arrest ◽  
Related Proteins ◽  
Dose Dependent

Lung cancer is among the most common malignancies with a poor 5-year survival rate reaching only 16%. Thus, new effective treatment modalities and drugs are urgently needed for the treatment of this malignancy. In this study, we conducted the first investigation of the effects of Biochanin A on lung cancer and revealed the mechanisms underlying its potential anticancer effects. Biochanin A decreased cell viability in a time-dependent and dose-dependent manner and suppressed colony formation in A549 and 95D cells. In addition, Biochanin A induced S phase arrest and apoptosis and decreased mitochondrial membrane potential (ΔΨm) in A549 and 95D cells in a dose-dependent manner. Our results of subcutaneous xenograft models showed that the growth of Biochanin A group was significantly inhibited compared with that of control groups. Finally, P21, Caspase-3, and Bcl-2 were activated in Biochanin A-treated cells and Biochanin A-treated xenografts which also demonstrated that Biochanin A induced cell cycle arrest and apoptosis in lung cancer cells by regulating expression of cell cycle-related proteins and apoptosis-related proteins. In conclusion, this study suggests that Biochanin A inhibits the proliferation of lung cancer cells and induces cell cycle arrest and apoptosis mainly by regulating cell cycle-related protein expression and activating the Bcl-2 and Caspase-3 pathways, thus suggesting that Biochanin A may be a promising drug to treat lung cancer.

scholarly journals Novel 1,3,4-oxadiazole Targets STAT3 Signaling to Induce Antitumor Effect in Lung Cancer

Biomedicines ◽  
2020 ◽  
Vol 8 (9) ◽  
pp. 368
Author(s):  
Vikas H. Malojirao ◽  
Swamy S. Girimanchanaika ◽  
Muthu K. Shanmugam ◽  
Ankith Sherapura ◽  
Dukanya ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Present Report ◽  
Lung Cancer Cells ◽  
Luciferase Reporter ◽  
Dependent Manner ◽  
Luciferase Reporter Gene ◽  
Stat3 Signaling ◽  
Ic50 Values

Lung cancer is the leading type of malignancy in terms of occurrence and mortality in the global context. STAT3 is an oncogenic transcription factor that is persistently activated in many types of human malignancies, including lung cancer. In the present report, new oxadiazole conjugated indazoles were synthesized and examined for their anticancer potential in a panel of cancer cell lines. Among the new compounds, 2-(3-(6-chloro-5-methylpyridin-3-yl)phenyl)-5-(1-methyl-1H-indazol-3-yl)-1,3,4-oxadiazole (CHK9) showed consistently good cytotoxicity towards lung cancer cells with IC50 values ranging between 4.8–5.1 µM. The proapoptotic effect of CHK9 was further demonstrated by Annexin-FITC staining and TUNEL assay. In addition, the effect of CHK9 on the activation of STAT3 in lung cancer cells was examined. CHK9 reduced the phosphorylation of STAT3Y705 in a dose-dependent manner. CHK9 had no effect on the activation and expression of JAK2 and STAT5. It also reduced the STAT3-dependent luciferase reporter gene expression. CHK9 increased the expression of proapoptotic (p53 and Bax) proteins and decreased the expression of the antiapoptotic (Bcl-2, Bcl-xL, BID, and ICAM-1) proteins. CHK9 displayed a significant reduction in the number of tumor nodules in the in vivo lung cancer model with suppression of STAT3 activation in tumor tissues. CHK9 did not show substantial toxicity in the normal murine model. Overall, CHK9 inhibits the growth of lung cancer cells and tumors by interfering with the STAT3 signaling pathway.

scholarly journals Synergy of nanodiamond–doxorubicin conjugates and PD-L1 blockade effectively turns tumor-associated macrophages against tumor cells

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Hua-Zhen Xu ◽  
Tong-Fei Li ◽  
Chao Wang ◽  
Yan Ma ◽  
Yan Liu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Tumor Cell ◽  
Cancer Cells ◽  
Tumor Cells ◽  
Lung Cancer Cells ◽  
Dependent Manner ◽  
Tumor Associated Macrophages ◽  
M1 Type

Abstract Background Tumor-associated macrophages (TAMs) are the most abundant stromal cells in the tumor microenvironment. Turning the TAMs against their host tumor cells is an intriguing therapeutic strategy particularly attractive for patients with immunologically “cold” tumors. This concept was mechanistically demonstrated on in vitro human and murine lung cancer cells and their corresponding TAM models through combinatorial use of nanodiamond-doxorubicin conjugates (Nano-DOX) and a PD-L1 blocking agent BMS-1. Nano-DOX are an agent previously proved to be able to stimulate tumor cells’ immunogenicity and thereby reactivate the TAMs into the anti-tumor M1 phenotype. Results Nano-DOX were first shown to stimulate the tumor cells and the TAMs to release the cytokine HMGB1 which, regardless of its source, acted through the RAGE/NF-κB pathway to induce PD-L1 in the tumor cells and PD-L1/PD-1 in the TAMs. Interestingly, Nano-DOX also induced NF-κB-dependent RAGE expression in the tumor cells and thus reinforced HMGB1’s action thereon. Then, BMS-1 was shown to enhance Nano-DOX-stimulated M1-type activation of TAMs both by blocking Nano-DOX-induced PD-L1 in the TAMs and by blocking tumor cell PD-L1 ligation with TAM PD-1. The TAMs with enhanced M1-type repolarization both killed the tumor cells and suppressed their growth. BMS-1 could also potentiate Nano-DOX’s action to suppress tumor cell growth via blocking of Nano-DOX-induced PD-L1 therein. Finally, Nano-DOX and BMS-1 achieved synergistic therapeutic efficacy against in vivo tumor grafts in a TAM-dependent manner. Conclusions PD-L1/PD-1 upregulation mediated by autocrine and paracrine activation of the HMGB1/RAGE/NF-κB signaling is a key response of lung cancer cells and their TAMs to stress, which can be induced by Nano-DOX. Blockade of Nano-DOX-induced PD-L1, both in the cancer cells and the TAMs, achieves enhanced activation of TAM-mediated anti-tumor response. Graphic abstract

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