膠質母細胞瘤是成人中最常見的原發性中樞神經系統 (CNS) 惡性腫瘤，由於其高侵襲度和低存活率，因此平均壽命大約落在15個月。然而，膠質母細胞瘤遷移過程中將會受到持續拉伸的機械刺激以及重複拉伸的機械刺激，由於目前尚未釐清細胞受到機械刺激後對細胞的機械轉導的影響，因此需要進一步的研究來探索其病理生理機制和治療方法。其中，細胞機械轉導涉及到細胞對外界的機械刺激的感知、傳導和轉化，並對腫瘤細胞的增殖、侵襲和轉移具有重要的影響。因此，研究持續拉伸及重複拉伸的皮牛頓力刺激對膠質母細胞瘤細胞的機械轉導影響，將有助於深入了解其病理生理機制，為後續治療提供理論支持。
在本研究中，使用膠質母瘤細胞(U87)作為細胞模型，證明了當細胞受到11.5 piconewton (pN)的持續拉伸及重複拉伸刺激後，細胞內的活性氧增加。細胞受力後，使細胞膜上的Piezo1打開，細胞外的鈣離子進入細胞內，並且藉由重複拉伸的機械刺激可以使細胞內的鈣離子累積。鈣離子進入細胞內後，使粒線體內的活性氧增加。細胞骨架中的肌動蛋白(F-actin)不論受到持續拉伸或者是重複拉伸刺激後會使細胞內的F-actin增生及重塑，增加細胞的抗拉強度；然而，當細胞膜受到持續拉伸刺激6秒或者是重複拉伸刺激總時長為6秒刺激後，會使磁珠下方區域的F-actin具有方向性，有助於細胞運動方向的定位。而在重複刺激總時長為30秒後，F-actin卻不具方向性，推測F-actin受到破壞，進而影響後續細胞遷移的能力。進一步抑制細胞骨架中的肌球蛋白II (Myosin II)觀察細胞骨架與機械刺激的關係，可以發現持續拉伸刺激時，抑制Myosin II並不會影響鈣離子進入細胞內，卻會使重複拉伸刺激後鈣離子累積增加。最後，當Piezo1受到抑制後會使細胞內鈣離子變化減少，卻在重複拉伸的機械刺激後得到鈣離子累積的結果呈現，驗證細胞內部分鈣離子變化來源於Piezo1。
總而言之，我們針對膠質母細胞瘤細胞的機械轉導進行了深入的探索，發現不同拉伸方法的機械刺激對細胞具有不同的影響。此外，研究也證明了機械刺激會使細胞外的離子進入細胞內，進而導致細胞內的活性氧產生，其中部分鈣離子可藉由Piezo1通道進入細胞內部，促使粒線體的活性氧增加，並且對細胞骨架及肌動蛋白的增生、重塑以及收縮力等方面產生了重要的影響。未來的研究可以進一步探討機械刺激與膠質母細胞瘤的生長、轉移等方面的關聯性，並且提供更有效的治療方法。

Glioma is the most common primary central nervous system (CNS) malignancy in adults. Despite the gradual improvement of medical standards, the average life expec-tancy is about 15 months, so prolonging the survival time is the primary goal. When cells are stimulated by external force, mechanosensitive receptors will convert the me-chanical force into chemical or electrical signals, causing the cells to produce physio-logical responses. In the human body, after the formation of glioblastoma, it will be me-chanically stimulated by the tensile stress generated between the tumor periphery and tumor core, the blood flow in capillaries in the tumor, or the deformation of the cell membrane caused by the change of cell volume during the process of cell migration. Therefore, understanding the physical properties of cancer cells is of great significance for cancer treatment and prevention.
In this study, using glioblastoma cells (U87) as a cell model, it was demonstrated that when the cells were stimulated by sustained stretching and cyclic stretching of 11.5 piconewton (pN), the reactive oxygen species in the cells increased. After the cells are stretched, Piezo1 on the cell membrane is opened, extracellular Ca 2+ enter the cells, and the mechanical stimulation of cyclic stretching can accumulate Ca 2+ in the cells. After Ca 2+ enter the cell, the active oxygen in the mitochondria increases. Whether the F-actin in the cytoskeleton is stimulated by sustained stretching or cyclic stretching, the F-actin in the cell will proliferate and remodel, increasing the tensile strength of the cell. However, when the cell membrane is stimulated by sustained stretching for 6 seconds or cyclic stretching for a total duration of 6 seconds, the F-actin in the area below the magnetic beads will have directionality, which will help to locate the direction of cell movement. However, after 30 seconds of cyclic stimulation, F-actin has no directionali-ty. It is speculated that F-actin is damaged, which in turn affects the ability of subse-quent cell migration. Further inhibit Myosin II in the cytoskeleton to observe the rela-tionship between the cytoskeleton and mechanical stimulation, it can be found that the inhibition of Myosin II will not affect the entry of Ca 2+ into the cells during sustained stretching stimulation, but it will reduce the contraction force in the cells, cause greater cell membrane deformation, and increase the accumulation of Ca 2+ after cyclic stretch-ing stimulation. Finally, when Piezo1 was inhibited, the change of intracellular Ca 2+ was reduced, but the results of Ca 2+ accumulation were obtained after cyclic stretching mechanical stimulation.
In summary, we conducted an in-depth exploration of mechanotransduction in glio-blastoma cells, and found that mechanical stimulation with different stretching methods had different effects on cells. In addition, studies have also proved that mechanical stimulation can cause extracellular cations to enter the cell, which in turn leads to the generation of reactive oxygen species in the cell. Part of Ca 2+ can enter the cell through the Piezo1 channel, which promotes the increase of reactive oxygen species in the mito-chondria, and it has an important impact on the proliferation, remodeling and contractil-ity of cytoskeleton and F-actin. Future research can further explore the relationship be-tween mechanical stimulation and the growth and metastasis of glioblastoma, and pro-vide more effective treatment methods.

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