Nanoparticles overcome adaptive immune resistance and enhance immunotherapy via targeting tumor microenvironment in lung cancer.

Lung cancer is one of the common malignant cancers worldwide. Immune checkpoint inhibitor (ICI) therapy has improved survival of lung cancer patients. However, ICI therapy leads to adaptive immune resistance and displays resistance to PD-1/PD-L1 blockade in lung cancer, leading to less immune response of lung cancer patients. Tumor microenvironment (TME) is an integral tumor microenvironment, which is involved in immunotherapy resistance. Nanomedicine has been used to enhance the immunotherapy in lung cancer. In this review article, we described the association between TME and immunotherapy in lung cancer. We also highlighted the importance of TME in immunotherapy in lung cancer. Moreover, we discussed how nanoparticles are involved in regulation of TME to improve the efficacy of immunotherapy, including Nanomedicine SGT-53, AZD1080, Nanomodulator NRF2, Cisplatin nanoparticles, Au@PG, DPAICP@ME, SPIO NP@M-P, NBTXR3 nanoparticles, ARAC nanoparticles, Nano-DOX, MS NPs, Nab-paclitaxel, GNPs-hPD-L1 siRNA. Furthermore, we concluded that targeting TME by nanoparticles could be helpful to overcome resistance to PD-1/PD-L1 blockade in lung cancer.

Lysionotin Induces Ferroptosis to Suppress Development of Colorectal Cancer via Promoting Nrf2 Degradation.

Extensive use of substances derived from natural sources has been documented in the treatment of colorectal cancer (CRC). Lysionotin (Lys) is a flavonoid present in the flowers and leaves of Gesneriaceae family plants. Despite its various pharmacological properties, which include neuroprotective, pro, antimalarial, and anticancer effects, the therapeutic advantages of Lys for CRC remain uncertain. In this present study, we demonstrated that Lys treatment successfully inhibited cell proliferation, migration, and invasion in HCT116 and SW480 CRC cells in vitro. Intriguingly, significant ferroptosis and reactive oxygen species (ROS) accumulation in CRC cells were induced by Lys treatment, whereas antagonism of ferroptosis by Liproxstatin-1 (Lip1) pretreatment retarded the anti-CRC effects of Lys. In addition, Lys reduced the amount of Nrf2 protein in CRC cells by increasing the rate at which it is degraded. Overexpression of Nrf2 rescued Lys reduced ferroptosis, suggesting the Nrf2 signaling is a crucial determinant of whether Lys induces ferroptosis in CRC cells. We also revealed that Lys suppressed tumor growth in vivo without obvious adverse effects on the main organs of mice. In conclusion, our results discovered that Lys treatment induced ferroptosis to exert antitumor effects in HCT116 and SW480 CRC cells by modulating Nrf2 signaling, providing a potential therapeutic approach for the prevention of colorectal cancer.

Dysregulation of MiR-144-5p/RNF187 Axis Contributes To the Progression of Colorectal Cancer.

Background and Objectives: RING finger protein 187 (RNF187) belongs to RING domain-containing E3 ligases family, which was recently reported to be involved in oncogenesis and development of several cancers. This research aims to clarify the role of RNF187 in colorectal cancer (CRC) development. Methods: The expression of RNF187 and miR-144-4p were determined by quantitative real-time polymerase chain reaction (qRT-PCR). The levels of RNF187 protein were assessed by western blot analysis. Cell Counting Kit-8 (CCK8) assay, clonogenic assay, cell scratch test and transwell assay were used to determine the proliferation, migration and invasion of CRC cells in vitro. The binding of miR-144-5p and RNF197 mRNA was validated by luciferase reporter assays. Tumor-bearing nude mice were used to determine CRC cells growth in vivo. Results: RNF187 expression significantly increased in CRC specimens and cell lines compared to normal colon tissues and normal colonic mucosa cell line, respectively. Upregulation of RNF187 expression was inversely correlated to poor prognosis in CRC patients. In addition, knockdown of RNF187 expression inhibited the proliferation, migration, and invasion but promoted the apoptosis of CRC lines Caco-2 and SW480 cells. Further studies validated that RNF187 was the direct target of miR-144-5p. The expression of miR-144-5p was downregulated in CRC tissues, which was negatively correlated to the expression of RNF187. Restoration of miR-144-5p significantly inhibited the progression of CRC cells and its anti-tumor effects could be abrogated by overexpression of RNF187. Conclusion: Our findings demonstrate the deregulation of miR-144-5p/ RNF187 axis in CRC, as well as its role in regulation of the tumor progression, thus providing a novel therapeutic strategy for CRC treatment.