The adjuvant value of Andrographis paniculata in metastatic esophageal cancer treatment – from preclinical perspectives

Abstract

Esophageal cancer (EC) is the fourth and sixth leading cause of cancer-related deaths in China and United States, respectively. The dismal prognosis of EC is mainly attributed to distant metastases, which may not be overcome by chemotherapy alone. Hence, the use of alternative adjuvant treatments, such as herbal medicines, for metastatic EC remains a great desire of patients. Our previous study demonstrated the in vivo anti-tumor and in vitro anti-invasion activities of Andrographis paniculata (AP) in esophageal cancer. In the present study, the chemical constituents of absorbed AP components through human intestinal Caco-2 cell monolayer were verified for the first time. The anti-migratory activities and suppressive effects on metastasis-related factors such as HER2, MMP2, MMP9, TM4SF3, CXCR4 of the absorbed AP components were revealed in esophageal cancer cells EC-109. The anti-tumor and anti-metastatic effects of AP water extract (1600 mg/kg) were further confirmed in metastatic esophageal xenograft-bearing mice. Besides, AP water extract acted synergistically with cisplatin plus 5-fluorouracil on inhibiting tumor nodule growth (with combination index <0.7). Meanwhile, chemotherapeutics-induced side-effects could also be reduced by AP water extract. The present findings provide evidence on safety and advantages of the combined use of AP with chemotherapeutics in pre-clinical setting.

Gene expression profiling reveals the plausible mechanisms underlying the antitumor and antimetastasis effects of Andrographis paniculata in esophageal cancer

“…The proportion of EC patients with EGFR overexpression ranges from 36.6% to 97%, and such overexpression is associated with lymph node metastasis, survival rate, and pathologic tumor stages (Zhang et al, ). The present data showed the reduced EGFR gene expression in APW‐treated cells as well as the decreased level of HER2 gene and protein after APW exposure as demonstrated in our previous study (Li et al, ), suggesting that ErbB signaling pathway is also contributed to the inhibitory effects of APW. Besides, the overexpression of PDGFRB enhanced the EC cell proliferation and migration ability through multiple signaling pathways (Song et al, ), and APW could down‐regulate such expressions.…”

“…The overexpression of ABC transporters are known for conferring multidrug resistance, which can elevate efflux of drugs from cancer cells, thereby diminish intracellular drug concentration (Hu et al, ; Sun, Patel, Kumar, & Chen, ). Our previous in vivo study showed that APW treatment enhanced the inhibitory effects of cisplatin plus 5‐FU on tumor growth (Li et al, ). APW also acted synergistic inhibitory effects with cisplatin and 5‐FU on motility of cancer cells in vitro (data not shown).…”

“…The powder of AP aqueous extract (APW) was stored in desiccators at 4 °C prior to the studies. The chemical profile of APW was registered as shown in our previous report (Li et al, ). APW was dissolved in culture medium and then filtered with 0.2‐μm filter for further bioassays.…”

“…Human esophageal squamous carcinoma cells EC‐109 were purchased from Cell Bank of Type Culture Collection of Chinese Academy of Sciences (Beijing, China). The culture condition was according to our previous studies (Li et al, ). In brief, EC‐109 cells were cultured in RPMI 1640 medium supplemented with 10% ( v /v) heat‐inactivated fetal bovine serum, 100‐U/ml penicillin, and 10‐U/ml streptomycin (Life Technology, USA).…”

“…The chemical profile of APW was registered as shown in our previous report (Li et al, 2017). APW was dissolved in culture medium and then filtered with 0.2-μm filter for further bioassays.…”