Ridgway P F, Smith A, Ziprin P, Jones T L, Paraskeva P A, Peck D H, Darzi A W
Department of Surgical Oncology and Technology, Imperial College School of Medicine, St. Mary's Hospital, 10th Floor QEQM Wing, Praed Street, London W2 1NY, United Kingdom.
Surg Endosc. 2002 Mar;16(3):533-6. doi: 10.1007/s00464-001-8311-7. Epub 2001 Nov 30.
Certain surgical strategies, including Helium (He) and carbon dioxide (CO2) insufflation in laparoscopy, have been shown to induce a hypoxic environment. This may have a significant effect on the invasive capacity of tumor cells and may be a factor in the incidence of port-site metastases seen in patients following laparoscopic resection for malignancy.
A colon adenocarcinoma cell line (SW1222) was exposed to an in vitro pneumoperitoneum of CO2 or He at 3 mmHg or left in normal growth conditions (control). After a 4-hour exposure to an in vitro pneumoperitoneum, the ability of the cells to invade through 8.0-microm Transwell filters coated with Matrigel was analyzed by colorimetric MTS assay and by direct staining of the filters. The effect of the addition of a known blocker of matrix metalloproteinases (MMPs), 1,10-phenanthroline (1,10-P), was investigated.
Cells exposed to an in vitro pneumoperitoneum demonstrate significantly increased invasive capacity compared to the control set, without loss of viability (He vs control, p <0.001; CO2 vs control, p <0.001). This augmented capacity is abolished by the addition of 1,10-P (p <0.01).
Exposure of a colonic adenocarcinoma cell line to either a CO2 or He pneumoperitoneum causes an increase in tumor cell invasiveness, which is abolished by the presence of a known inhibitor of MMPs. This suggests that MMPs have an important role in the metastatic potential of tumors exposed to a hypoxic operative environment.
某些手术策略，包括腹腔镜手术中的氦气（He）和二氧化碳（CO₂）气腹，已被证明会诱导低氧环境。这可能对肿瘤细胞的侵袭能力产生显著影响，并且可能是恶性肿瘤患者腹腔镜切除术后出现切口转移发生率的一个因素。
将结肠腺癌细胞系（SW1222）暴露于3 mmHg的CO₂或He体外气腹环境中，或置于正常生长条件下（对照组）。在体外气腹暴露4小时后，通过比色MTS分析和对滤膜进行直接染色，分析细胞穿过涂有基质胶的8.0微米Transwell滤膜的侵袭能力。研究了添加已知的基质金属蛋白酶（MMPs）阻滞剂1,10 - 菲咯啉（1,10 - P）的效果。
与对照组相比，暴露于体外气腹环境的细胞显示出显著增强的侵袭能力，且活力未丧失（He组与对照组相比，p <0.001；CO₂组与对照组相比，p <0.001）。添加1,10 - P可消除这种增强的能力（p <0.01）。
结肠腺癌细胞系暴露于CO₂或He气腹环境会导致肿瘤细胞侵袭性增加，而已知的MMPs抑制剂可消除这种增加。这表明MMPs在暴露于低氧手术环境的肿瘤转移潜能中起重要作用。
