School of Life Sciences, Hainan University, No. 58 Renmin Avenue, Haikou, 570228, China.
Department of Physiology, Hainan Medical University, Haikou, China.
BMC Complement Med Ther. 2022 May 4;22(1):123. doi: 10.1186/s12906-022-03612-2.
Bacteria-mediated cancer immunotherapy (BCI) robustly stimulates the immune system and represses angiogenesis, but tumor recurrence and metastasis commonly occur after BCI. The natural product Ilex kudingcha C. J Tseng enriched with ursolic acid has anti-cancer activity and could potentially augment the therapeutic effects of BCI. The objective of the present study was to determine potential additive effects of these modalities.
We investigated the anti-cancer activity of KDCE (Kudingcha extract) combined with S.t△ppGpp in the mice colon cancer models.
In the present study, KDCE combined with S.t△ppGpp BCI improved antitumor therapeutic efficacy compared to S.t△ppGpp or KDCE alone. KDCE did not prolong bacterial tumor-colonizing time, but enhanced the antiangiogenic effect of S.t△ppGpp by downregulatingVEGFR2. We speculated that KDCE-induced VEGFR2 downregulation is associated with FAK/MMP9/STAT3 axis but not AKT or ERK.
Ursolic acid-enriched KDCE enhances the antitumor activity of BCI, which could be mediated by VEGFR2 downregulation and subsequent suppression of angiogenesis. Therefore, combination therapy with S.t△ppGpp and KDCE is a potential cancer therapeutic strategy.
细菌介导的癌症免疫疗法（BCI）能强有力地刺激免疫系统并抑制血管生成，但 BCI 后肿瘤复发和转移仍很常见。富含熊果酸的天然产物 Ilex kudingcha C. J Tseng 具有抗癌活性，可能增强 BCI 的治疗效果。本研究旨在确定这些方法的潜在附加效应。
我们在小鼠结肠癌模型中研究了 KDCE（苦丁茶提取物）与 S.t△ppGpp 联合的抗癌活性。
在本研究中，与 S.t△ppGpp 或 KDCE 单独治疗相比，KDCE 联合 S.t△ppGpp BCI 提高了抗肿瘤治疗效果。KDCE 并未延长细菌在肿瘤中的定植时间，但通过下调 VEGFR2 增强了 S.t△ppGpp 的抗血管生成作用。我们推测，KDCE 诱导的 VEGFR2 下调与 FAK/MMP9/STAT3 轴有关，但与 AKT 或 ERK 无关。
富含熊果酸的 KDCE 增强了 BCI 的抗肿瘤活性，这可能是通过下调 VEGFR2 并随后抑制血管生成介导的。因此，S.t△ppGpp 和 KDCE 的联合治疗是一种潜在的癌症治疗策略。
