重楼增强麦门冬汤抗肺癌转移的疗效

Maimendong decoction (MMDD), a classic traditional Chinese medicine (TCM) formula prescribed for lung atrophy , has demonstrated efficacy against various pulmonary disorders. Our prior research confirmed that MMDD inhibit lung cancer metastasis by modulating natural killer (NK) cells. Paris polyphylla (P.P), a TCM herb with known anti-tumor properties, is often incorporated into classic formulas to enhance therapeutic outcomes. This study aimed to boost the anti-metastatic efficacy of MMDD against lung cancer by incorporating Paris polyphylla (Chonglou) and to investigate the underlying mechanisms.

The Modified Maimendong Decoction (MMDD + P.P) Was Prepared by Adding 9 18 g of Paris polyphylla. Its Effects on the proliferation, migration, and Apoptosis of CTC-TJH-01 and LLC Cells Were Assessed Using CCK-8, Transwell, and Annexin V-FITC/PI Flow Cytometry assays. Apoptosis-related Proteins Were Analyzed by Western blot. A Tail Vein injection-induced Lung Metastasis Model in C57BL/6 Mice Was Established To Evaluate the Effects of MMDD + P.P, both Alone and in Combination with an anti-PD-1 antibody, on Metastasis Flow cytometry was used to profile T cell and NK cell populations in peripheral blood. Histological and molecular analyses of metastatic tissues were performed using H&E staining, immunohistochemistry (for Ki-67 and cleaved caspase-3), and immunofluorescence (for CD8+ T cell and NK cell infiltration).

Compared to MMDD alone, MMDD + P.P (18 g) significantly inhibited proliferation and migration, and induced apoptosis in both CTC-TJH-01 and LLC cells. These effects were associated with the upregulation of pro-apoptotic proteins (cleaved caspase-3, BAX, cleaved PARP) and downregulation of anti-apoptotic proteins (BCL-2, Survivin). In vivo, while both MMDD and MMDD + P.P reduced the number of lung metastatic nodules, MMDD + P.P (18 g) was uniquely effective in significantly reducing overall tumor burden, which correlated with decreased Ki-67 and increased cleaved caspase-3 in metastatic foci. Furthermore, MMDD + P.P (18 g) significantly increased the proportions and tumor-infiltration of NK cells and CD8+ T cells. It also synergized with anti-PD-1 therapy, enhancing its anti-metastatic effect and boosting the expression of cytotoxic markers (CD107a, perforin, granzyme B) and TNF- in CD8+ T cells.

Incorporating Paris polyphylla into MMDD enhances its anti-metastatic efficacy through a dual mechanism: directly inducing apoptosis in lung cancer cells and amplifying anti-tumor immunity by increasing the abundance and cytotoxic function of CD8+ T cells. The synergy between MMDD + P.P and anti-PD-1 antibody therapy highlights the potential of this modified TCM formula as a promising adjunctive treatment for inhibiting lung cancer metastasis.