Objective: Acetyl-11-keto-β-boswellic acid (AKBA) is a triterpenoid, which is the main component of boswellic acid from Boswellia Serrata, a medicinal plant that has shown immense potential in anti-cancer therapy. This study aims to explore the roles and molecular mechanisms of AKBA on cell behavior in non-small cell lung cancer (NSCLC) cells. Materials and Methods: The effects of AKBA on the cell viability in A549, H460, H1299, and BEAS-2B cells were determined by the CCK-8 assay. The colony formation assay was used to identify the effects of AKBA on cell proliferation. Potential roles of AKBA in regulating the cell cycle, apoptosis, and autophagy in A549 were evaluated by flow cytometry, Western blotting, reverse transcription-polymerase chain reaction (PCR) and immunofluorescence (IF). Results: AKBA reduced cell viability in A549, H460, H1299, and BEAS-2B. In A549 cells, AKBA suppressed the clone formation, arrested the cell cycle at the G 0 /G 1 phase, induced cellular apoptosis. We found that AKBA suppressed the formation of autolysosome, and decreased the expression levels of Beclin-1, LC3A/B-I, and LC3A/B-II proteins. Furthermore, AKBA also inhibited the expression levels of PI3K/Akt signaling pathway proteins. Conclusion: AKBA exerts the anti-cancer effects via cell cycle arrest, apoptosis induction, and autophagy suppression in NSCLC cells. This body of evidence supports the potential of AKBA as a promising drug in the treatment of NSCLC.

Conclusion: Nomograms were used to comprehensively calculate independent factors to determine which treatment (radiotherapy or surgery) is better for each patient. A website was used to offer guidance regarding surgery or radiation for patients and physicians.

Fluoxetine, one of the latest clinical antidepressants, is reported to have the anti-proliferative effect on cancer cells via immune-related pathways. However, the mechanism is still not known. This study mainly focused on the discovery of the molecular basis of the inhibitory effect of fluoxetine in lung cancer. The specific anti-proliferation effect and autophagy induced by fluoxetine on lung cancer cell were shown in CCK8 and immunofluorescence. The RNA sequence hinted that the endoplasmic reticulum (ER) stress-related protein and mTOR pathway were enriched after fluoxetine treatment. Western blot results revealed that the ER stress pathway was activated by fluoxetine, including PERK, ATF4, and CHOP, while the AKT/mTOR pathway was inhibited. In addition, the transfection of ATF4 siRNA further discovered that ER stress participated in the inhibition of AKT/mTOR pathway and the induction of anti-proliferation and autophagy in the fluoxetine-treated cells. More importantly, fluoxetine was demonstrated to play cytotoxic activity in cancer cells without affecting normal cells. Our results showed that fluoxetine triggered the ATF4-AKT-mTOR signaling pathway to induce cell cycle arrest and autophagy restraining cancer cells’ growth in lung cancer. This study found fluoxetine unaffected the proliferation of normal lung epithelial cells, providing safe clinical therapeutic strategies for lung cancer patients with depression.

BackgroundRecent studies showed that myeloid-derived suppressor cells (MDSCs) and M2-like macrophages are involved in the treatment of non-small cell lung cancer (NSCLC) as immunosuppressive cells; however, the changes of MDSCs and M2-like macrophages, and their prognostic value are rarely unknown in NSCLC patients during radiotherapy. In this article, we aim to explore dynamic alteration of the circulating MDSCs and M2-like macrophages, to examine their relationship, and to evaluate their prognostic value for NSCLC patients in radiotherapy.Method:Peripheral blood mononuclear cells from healthy controls and NSCLC patients in radiotherapy were isolated to examine the circulating MDSCs and M2-like macrophages. The peripheral MDSCs defined as CD11b+CD33+HLA-DR− and M2-like Macrophages signified as CD68+CD163+ were determined by flow cytometry. 40 plasma inflammatory cytokines were measured by multiplex ELISA.ResultsCompared with health controls, the percentages of MDSCs and CD68+CD163+M2-like macrophages of NSCLC patients were significantly elevated, and were distinctly higher in NSCLC patients in radiotherapy than in pre-radiotherapy. Moreover, MDSCs correlated positively with CD68+CD163+M2-like macrophages in NSCLC patients in radiotherapy and post-radiotherapy. Interestingly, the alterations of the percentages of MDSCs and CD68+CD163+M2-like macrophages in RT were irrelated with radiotherapy area. During radiotherapy, the proportions of MDSCs were clearly increased in adenocarcinoma patients but not in squamous carcinoma patients, while the proportions of CD68+CD163+M2-like macrophages were markedly elevated in squamous carcinoma patients but not in adenocarcinoma patients. In addition, the percentages of MDSCs and CD68+CD163+ M2-like macrophages were also increased in NSCLC patients reached PR in radiotherapy compared to NSCLC patients reached SD and PD. IL-1ra and MIP-1β have a positive relation with MDSCs or M2 macrophages in NSCLC patients in radiotherapy, and Eotaxin was correlated with CD68+CD163+M2-like macrophages but not MDSCs in NSCLC patients after radiotherapy.ConclusionsThe dynamic alterations of MDSCs and M2-like macrophages, as well as their connection with plasm inflammation cytokines, could provide potentially prognostic and sensitive markers for NSCLC patients in radiotherapy.Trial Registration: Jinshan Hospital of Fudan University, IEC-2020-S01. Registered 22 May 2020.

Background. Recent studies show that myeloid-derived suppressor cells (MDSCs) and M2-like macrophages are involved in the treatment of tumors; however, their therapeutic response role is rarely known in non-small cell lung cancer (NSCLC) during radiotherapy. We aim to explore the dynamic alteration of the circulating MDSCs and M2-like macrophages, to examine their relationship, and to evaluate their therapeutic response value for NSCLC patients in radiotherapy. Methods. Peripheral blood mononuclear cells from healthy controls and NSCLC patients with different radiotherapy phases were isolated to examine the circulating MDSCs and M2-like macrophages by flow cytometry. 40 plasma inflammatory cytokines were measured by multiplex ELISA. Results. In comparison with healthy controls, the percentages of MDSCs and CD68+CD163+M2-like macrophages of NSCLC patients were significantly elevated and were distinctly higher in radiotherapy than in preradiotherapy. MDSCs were correlated positively with CD68+CD163+M2-like macrophages in NSCLC patients in radiotherapy and postradiotherapy. Especially, we found that in comparison with those in the poor group, the percentages of two cells in the good response group were markedly increased during radiotherapy and they had a significantly positive correlation. During radiotherapy, the proportions of MDSCs were clearly increased in adenocarcinoma patients and the percentages of CD68+CD163+M2-like macrophages were markedly elevated in squamous carcinoma patients. We found that after radiotherapy, the expressions of eotaxin, MIP-1β, MCP-1, and BLC were significantly increased in NSCLC patients. Further results showed that the low levels of eotaxin and TNF RII expression before radiotherapy could predict a good therapeutic response. IL-1ra and MIP-1β had a positive relation with MDSCs or CD68+CD163+M2-like macrophages in NSCLC patients during radiotherapy, and eotaxin was correlated with CD68+CD163+M2-like macrophages but not MDSCs in NSCLC patients after radiotherapy. Conclusions. MDSCs and CD68+CD163+M2-like macrophages serve as therapeutic response biomarkers and are associated with the expressions of plasma inflammatory cytokines for NSCLC patients during radiotherapy.