Sophoridine Inhibits the Tumour Growth of Non-Small Lung Cancer by Inducing Macrophages M1 Polarisation via MAPK-Mediated Inflammatory Pathway

Abstract

Lung cancer is one of the most common and lethal neoplasms for which very few efficacious treatments are currently available. M1-like polarised tumour-associated macrophages (TAMs) are key mediators to modulate the tumour microenvironment, which play a key role in inhibiting cancer cell growth. Sophoridine, a naturally occurring alkaloid, exerts multiple pharmacological activities including anti-tumour and anti-inflammatory activities, but it has not been characterised as a regulator of tumour microenvironment towards NSCLC. Herein, the regulatory effects of sophoridine on the polarisation of THP-1 cells into TAMs and the anti-tumour effects of sophoridine-stimulated M1 polarised macrophages towards lung cancer cells were carefully investigated both in vitro and in vivo. The results showed that sophoridine could significantly promote M1 polarisation of RAW264.7 and THP-1-derived macrophages, leading to increased expression of pro-inflammatory cytokines and the M1 surface markers CD86 via activating MAPKs signaling pathway. Further investigations showed that sophoridine-stimulated RAW264.7 and THP-1-derived M1 macrophages effectively induced cell apoptosis as well as inhibited the cell colony formation and cell proliferation in both H460 and Lewis lung cancer cells. In Lewis-bearing mice model, sophoridine (15 or 25 mg/kg) significantly inhibited the tumour growth and up-regulated the expression of CD86/F4/80 in tumour tissues. Collectively, the findings clearly demonstrate that sophoridine promoted M1-like polarisation in vitro and in vivo, suggesting that sophoridine held a great therapeutic potential for treating lung cancer.

Cordyceps sinensis relieves non-small cell lung cancer by inhibiting the MAPK pathway

“…Lung cancer cells recruit monocytes, neutrophils, and other WBCs by secreting various mediators, thereby producing a series of inflammatory factors [ 25 ]. Reactive oxygen species (ROS), the oxidative product of cell metabolism, damages lipid, nucleic acid, and protein function, breaks the oxidative balance, induces oxidative stress, and promotes inflammation, all of which lead to various diseases [ 26 , 27 ].…”

Cucurbitacin B Controls M2 Macrophage Polarization to Suppresses Metastasis via Targeting JAK-2/STAT3 Signalling Pathway

“…Therefore, reprogramming of M2-like macrophage toward the antitumoral might be potential new therapeutic targets. More and more studies have indicated the mechanism of monomeric components of traditional Chinese medicine exert anti-tumor effect by modulating M1 or M2 macrophage polarization [33,34].…”

Research Progress in the Pharmacological Activities, Toxicities, and Pharmacokinetics of Sophoridine and Its Derivatives

“… 24 In Lewis mouse model, Zhao et al (2014) found that sophoridine (15 and 25 mg/kg) effectively inhibits tumor growth of non-small lung cancer by activating MAPKs signaling pathway and increasing expression of pro-inflammatory cytokines and M1 surface marker CD86. 25 …”

“…24 In Lewis mouse model, Zhao et al (2014) found that sophoridine (15 and 25 mg/kg) effectively inhibits tumor growth of non-small lung cancer by activating MAPKs signaling pathway and increasing expression of pro-inflammatory cytokines and M1 surface marker CD86. 25 Dong et al (2014) assessment of these properties revealed that mesoporous silica nanospheres effectively regulated the uptake and release of sophoridine; however, how these nanospheres perform in vivo remains unknown. 26 Inspired by the above ideas, Wang et al (2016) prepared sophoridine-loaded PLGA microspheres using the O/O emulsion-solvent evaporation method, which exhibited combined lung-targeting and sustained drug release properties.…”