The Affiliated Hospital of Chengde Medical University, Chengde 067000, Hebei, China.
The Affiliated Hospital of Chengde Medical University, Chengde 067000, Hebei, China.
Gene. 2020 Dec 15;762:145044. doi: 10.1016/j.gene.2020.145044. Epub 2020 Aug 7.
Gastric cancer is the most common malignant tumor. Most patients suffering from gastric cancer die of metastasis. The role of Atrial natriuretic peptide (ANP) in inhibiting and eliminating kinds of cancer cells has been reported. Aberrant activation of Hedgehog (Hh) signaling pathway contributes to initiation and progression of various malignancies. We have previously reported that the inhibitor of Hh, cyclopamine, reduces the metastatic activity of MGC-803 via inhibiting the expression of matrix metalloproteinases (MMP)-9. It remains to be further demonstrated that ANP has the suppressive effects on invasion and metastasis in gastric cancer via Hh-mediated MMP-9 production.
Transwell, western blot, qRT-PCR were used after application of ANP on MGC-803 gastric cancer cells to determine the levels of cell migration and invasion, protein levels of MMP-9 and Hh, as well as mRNAs of MMP-9 and Hh, respectively.
It was demonstrated that the migration and invasion were significantly lower, MMP-9 and Hh as well as their mRNAs were lower as well, in ANP-treated MGC-803 gastric cancer cells than those in control.
The expression of MMP-9 induced by aberrant activation of Hh in MGC-803 was inhibited by ANP, which may contribute to the inhibition of cell migration and invasion. These results suggested the potential of ANP to be used in gastric cancer therapy as an inhibitor targetting Hh signaling pathway to inhibit the proliferation as well as invasion and metastasis of gastric cancer.
胃癌是最常见的恶性肿瘤。大多数胃癌患者死于转移。已有报道称心房利钠肽（ANP）在抑制和消除各种癌细胞方面的作用。Hedgehog（Hh）信号通路的异常激活有助于各种恶性肿瘤的发生和发展。我们之前报道过，Hh 的抑制剂——环巴胺通过抑制基质金属蛋白酶（MMP）-9的表达，降低了 MGC-803 的转移活性。尚需进一步证明 ANP 通过 Hh 介导的 MMP-9 产生对胃癌的侵袭和转移具有抑制作用。
在应用 ANP 于 MGC-803 胃癌细胞后，通过 Transwell、Western blot 和 qRT-PCR 分别测定细胞迁移和侵袭水平、MMP-9 和 Hh 的蛋白水平以及 MMP-9 和 Hh 的 mRNAs。
结果表明，与对照组相比，ANP 处理的 MGC-803 胃癌细胞的迁移和侵袭明显降低，MMP-9 和 Hh 及其 mRNAs 水平也降低。
ANP 抑制了 Hh 异常激活诱导的 MGC-803 中 MMP-9 的表达，这可能有助于抑制细胞迁移和侵袭。这些结果表明，ANP 作为一种抑制 Hh 信号通路的靶点，具有抑制胃癌增殖以及侵袭和转移的潜力，可用于胃癌的治疗。
