ABSTRACT
Postoperative asymptomatic patients with early cancer (lung cancer) have dormant disseminated tumor cells (DTCs) in their metastatic target organs, and the proliferation of these DTCs is the key link leading to clinical metastasis. The development of therapeutic agents to maintain DTCs dormant or eradicate dormant DTCs will prevent tumor metastasis and break through the bottleneck of improving the overall efficacy of treating malignant tumors. This paper reviews the methods of establishing in vitro and in vivo research models of DTCs with dormant characteristics to promote the understanding of dormant DTCs and improve the research and development efficiency of anti-tumor metastasis drugs.
ABSTRACT
Objective To explore the effect of immune senescence on lung cancer metastasis and reveal the mechanism of Fuzheng traditional Chinese medicine Jinfukang in the prevention and treatment of the metastasis. Methods A lung metastasis model of Lewis lung cancer cells was established in C57BL/6 mice with different ages (15 months, 6 months, and 2 months). Mice in the 6-month-old group were given Jinfukang intragastrically for 42 days. Pulmonary metastasis was analyzed by in vivo imaging, anatomical microscopic observation, and HE staining. The proportion of memory T cells and NK cells in peripheral blood was detected by flow cytometry. Results The lung metastatic tumor formation rate of 15-month-old and 6-month-old mice was significantly higher than that of 2-month-old mice (all P < 0.05). Abundance of CD4+T cells in peripheral blood was positively correlated with age (2-month-old vs. 6-month-old, P=0.041; 2-month-old vs.15-month-old, P=0.041; 6-month-old vs.15-month-old, P=0.953). The abundance of NK cells was negatively correlated with age (2-month-old vs. 6-month-old, P=0.009; 2-month-old vs.15-month-old, P=0.009; 6-month-old vs. 15-month-old, P=0.574). However, the survival time of mice in the Jinfukang group was longer (P > 0.05) and the level of NK cells in peripheral blood was significantly higher (P=0.029) than those in the normal saline group. Conclusion Immune senescence can promote the metastasis of lung cancer. The prolongation of the survival time of mice administered with Jinfukang may be related to delaying immune senescence and increasing the number of NK cells.
ABSTRACT
The prevention and treatment of tumor metastasis can significantly improve the survival of patients with solid tumors. However, there is still a lack of effective drugs for the prevention and treatment of metastasis. The main reason is that the existing intervention and therapeutic drugs are difficult to achieve precise prevention and treatment of metastasis. Due to disseminated tumor cells (DTCs) already exist in the metastatic target organs of early postoperative patients, they are difficult to be detected with existing imaging techniques, and there is a lack of effective intervention drugs and efficacy evaluation systems. When DTCs grow to be detectable by imaging, the patient is already in the advanced stage of cancer, which has become a bottleneck restricting the breakthroughs in metastasis prevention and treatment. This paper reviews the dormancy and survival mechanism of DTCs in metastatic target organs and its intervention strategies, in order to promote the curative effect of metastasis prevention and treatment.
ABSTRACT
Metastasis is the main factor leading to the death of patients with lung cancer, and active prevention is the key to improve the efficacy of treatment. Circulating tumor cells (CTCs) play an important role in initiating metastasis. They trigger a series of metastatic cascade reactions at the moment of shedding from the primary focus, and finally colonize and proliferate in the distant target organs. In recent years, the detection technology of lung cancer CTCs has been continuously optimized. It can not only count CTCs, but also identify different subsets. CTCs detection of lung cancer can be used for early screening, the prediction of prognosis after surgery and chemoradiotherapy and the evaluation of curative effect of targeted immunotherapy. Dynamic monitoring of tumor heterogeneity is helpful to adjust personalized treatment plan and achieve the accurate treatment of cancer. Tian Jianhui's research group established the world's first circulating tumor cell line of human lung adenocarcinoma, integrated it into the theory of "positive deficiency and toxin" in the subclinical core pathogenesis of lung cancer, and actively promoted the construction of a specific research platform for lung cancer, in order to improve the research, prevention and control efficiency of lung cancer metastasis.
ABSTRACT
Objective: To explore the molecular mechanism of Jinfukang inducing the senescence of circulating tumor cells (CTCs) in patients with non-small cell lung cancer. Methods: Human lung cancer CTCs (CTC-TJH-01 cells) were treated with different concentrations (0, 125, 250, 500 and 1 000 μg/mL) of Jinfukang. The proliferation of CTC-TJH-01 cells was detected by CCK-8 assay. The state of cellular senescence was detected by β-galactosidase staining. The expression of proliferating cell nuclear antigen (PCNA) protein in CTC-TJH-01 cells was detected by flow cytometry and immunofluorescence staining. The expression levels of proliferation- and senescence-associated proteins including p16, p21, retinoblastoma protein (RB) and phospho-RB (p-RB) were detected by Western blotting. Results: Jinfukang inhibited the proliferation of CTC-TJH-01 cells (500 and 1 000 μg/mL: both P < 0.05), induced the senescence of CTC-TJH-01 cells (350 and 700 μg/mL: both P < 0.05), and promoted the expression of PCNA protein in CTC-TJH-01 cells (350 and 700 μg/mL: both P < 0.05). The expression levels of p16 and p21 proteins were up-regulated, but the expression level of p-RB protein was down-regulated after treatment (all P < 0.05). Conclusion: Jinfukang induces the senescence of CTCs by regulating p16/RB signal pathway, which may be the mechanism of preventing the recurrence and metastasis of lung cancer.
ABSTRACT
Circulating tumor cells (CTCs), as the seeds of tumor metastasis, manage to escape from immune clearance both in microen-vironment and in peripheral blood. CTCs can also facilitate formation of pre-existing environment, which is the crucial step in metasta-sis. Myeloid-derived suppressor cells (MDSC), as a group of immunosuppressive cells derived from bone marrow cells, may play a key role in this process. In this review, the progress in MDSC and its role in the formation, survival, and immune escape of CTCs were exten-sively discussed to explore a new target for tumor immunotherapy.